Adjuvant bisphosphonate treatment for breast cancer: why did something so elegant become so complicated?

PubMed

Clemons, Mark; Russell, Kent; Costa, Luis; Addison, Christina L

2012-07-01

Bisphosphonate therapy has revolutionized the care of patients with metastatic bone disease. With its demonstrated activity and anti-tumour effects in preclinical studies it was natural to transition these agents to testing in the adjuvant setting. Surprisingly, the results of adjuvant breast cancer trials have shown either modest or no benefit or even harm. We sought to explore whether there were specific patient cohorts or treatment strategies that were most likely to benefit from adjuvant bisphosphonate therapy. We compared trial designs, patient characteristics and outcomes from the six published and two presented randomized adjuvant bisphosphonate trials. Differences in trial design and patient populations make direct comparisons complicated. The most efficacious use of adjuvant bisphosphonates appears to be in patients with either biopsy evidence of osseous micrometastases, were post-menopausal or had estrogen receptor-positive tumours. Despite tremendous optimism regarding adjuvant bisphosphonate therapy, results from large trials are conflicting. Further investigation into factors influencing response to bisphosphonate treatment or selection of appropriate sub-groups of patients with desirable response characteristics is warranted.

Trends in the Utilization of Adjuvant Vaginal Cuff Brachytherapy and/or External Beam Radiation Treatment in Stage I and II Endometrial Cancer: A Surveillance, Epidemiology, and End-Results Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Mehul K.; Cote, Michele L.; Ali-Fehmi, Rouba

2012-05-01

Purpose: The optimal adjuvant radiation treatment for endometrial carcinoma (EC) remains controversial. Adjuvant vaginal cuff brachytherapy (VB) has emerged as an increasingly common treatment modality. However, the time trends for using VB, external beam radiation therapy (EBRT), or combined therapy (VB+EBRT) have not been well characterized. We therefore examined the utilization trends of VB, EBRT, and VB+EBRT for adjuvant RT in International Federation of Gynecologic Oncology (FIGO) stage I and II EC over time. Methods and Materials: We evaluated treatment patterns for 48,122 patients with EC diagnosed between January 1995 and December 2005, using the National Cancer Institute's Surveillance, Epidemiology,more » and End Results (SEER) public use database. Chi-squared tests were used to assess differences by radiation type (VB, EBRT, and VB+EBRT) and various demographic and clinical variables. Results: Analyses were limited to 9,815 patients (20.4%) with EC who met the inclusion criteria. Among women who received adjuvant RT, the proportion receiving VB increased yearly (12.9% in 1995 compared to 32.8% in 2005 (p < 0.0001). The increasing use of VB was proportional to the decreasing use of EBRT (56.1% in 1995 to 45.8% in 2005; p < 0.0001) and VB+EBRT (31.0% in 1995 to 21.4% in 2005; p < 0.001). Conclusions: This population-based report demonstrates an increasing trend in the use of VB in the adjuvant setting after hysterectomy for treatment of women with FIGO stage I-II EC. VB alone appears to be replacing pelvic EBRT and VB+EBRT therapy in the management of stage I-II EC.« less

Retrospective study of management of uterine sarcomas at Oxford 1990-1998: role of adjuvant treatment.

PubMed

Riddle, P J; Echeta, C B; Manek, S; Lavery, B A; Charnock, F M L; Mackenzie, I; Ganesan, T S

2002-02-01

We report a retrospective study of 47 consecutive patients with uterine sarcoma treated at the Churchill Hospital in Oxford between 1990-1998. The mainstay of treatment was surgery with adjuvant chemotherapy and radiotherapy reserved for selected patients with early stage disease. Overall 1 and 2 year survival was 49% and 30% respectively compared with 73% and 55% in the group who received adjuvant chemotherapy/radiotherapy. Median survival was 11 months for the group as a whole compared to 32.9 months in the adjuvant therapy group. This is a retrospective review with small numbers and considerable selection bias, however, given the poor survival of patients with this disease, adjuvant treatment should be considered in future trials of patients with uterine sarcoma.

Treatment modalities and evaluation models for periodontitis

PubMed Central

Tariq, Mohammad; Iqbal, Zeenat; Ali, Javed; Baboota, Sanjula; Talegaonkar, Sushama; Ahmad, Zulfiqar; Sahni, Jasjeet K

2012-01-01

Periodontitis is the most common localized dental inflammatory disease related with several pathological conditions like inflammation of gums (gingivitis), degeneration of periodontal ligament, dental cementum and alveolar bone loss. In this perspective, the various preventive and treatment modalities, including oral hygiene, gingival irrigations, mechanical instrumentation, full mouth disinfection, host modulation and antimicrobial therapy, which are used either as adjunctive treatments or as stand-alone therapies in the non-surgical management of periodontal infections, have been discussed. Intra-pocket, sustained release systems have emerged as a novel paradigm for the future research. In this article, special consideration is given to different locally delivered anti-microbial and anti inflammatory medications which are either commercially available or are currently under consideration for Food and Drug Administration (FDA) approval. The various in vitro dissolution models and microbiological strain investigated to impersonate the infected and inflamed periodontal cavity and to predict the in vivo performance of treatment modalities have also been thrashed out. Animal models that have been employed to explore the pathology at the different stages of periodontitis and to evaluate its treatment modalities are enlightened in this proposed review. PMID:23373002

Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agbahiwe, Harold C.; Wharam, Moody; Batra, Sachin

2013-02-01

Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves andmore » descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.« less

Continuation of Weight Loss Treatment Is Associated with the Number of Self-Selected Treatment Modalities

ERIC Educational Resources Information Center

Martin, Corby K.; Drab-Hudson, Danae L.; York-Crowe, Emily; Mayville, Stephen B.; Yu, Ying; Greenway, Frank L.

2007-01-01

Behavior therapy is a cornerstone of weight loss treatment and behaviorists help direct patients' treatment. A novel design was used that allowed participants to choose different treatment modalities during behavioral weight loss treatment. The association between the selection of different treatment modalities and program completion was examined…

Treatment modalities of palmoplantar lichen planus: a brief review.

PubMed

Feily, Amir; Yaghoobi, Reza; Nilforoushzadeh, Mohammad Ali

2016-12-01

Palmoplantar lichen planus is a localized and uncommon variant of lichen planus which is mostly resistant to treatment. Our purpose was to discuss all treatment modalities proposed and tested for palmoplantar lichen planus in the literature. A systematic review of the literature was conducted to evaluate evidence regarding all treatment modalities proposed and tested for palmoplantar lichen planus in the literature. Two major databases (PubMed, Google scholar) were searched. The review included all case reports, letters and original articles reporting any treatment for palmoplantar lichen planus but not treatment used in the other type of lichen planus, generalized lichen planus or other type of palmoplantar dermatoses. We have gone over more than 50 articles. There are many drugs that have been used in the treatment of lichen planus and generalized lichen planus but the palmoplantar type is a rare variety of lichen planus. That is why we could not find any clinical trial on the subject and just case reports have been described in this manuscript. In spite of plentiful investigations carried out on lichen planus, there is no treatment modality that has proved to be utterly satisfactory in treatment of palmoplantar lichen planus.

Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients.

PubMed

Allouchery, Violette; Beaussire, Ludivine; Perdrix, Anne; Sefrioui, David; Augusto, Laetitia; Guillemet, Cécile; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric; Clatot, Florian

2018-05-16

Detection of circulating ESR1 mutations is associated with acquired resistance to aromatase inhibitor (AI) in metastatic breast cancer. Until now, the presence of circulating ESR1 mutations at the end of adjuvant treatment by AI in early breast cancer had never been clearly established. In this context, the aim of the present study was to evaluate the circulating ESR1 mutation frequency at the end of adjuvant treatment and after relapse. This monocentric retrospective study was based on available stored plasmas and included all early breast cancer patients who completed at least 2 years of AI adjuvant treatment and experienced a documented relapse after the end of their treatment. Circulating ESR1 mutations (D538G, Y537S/N/C) were assessed by droplet digital PCR in plasma samples taken at the end of adjuvant treatment, at time of relapse and at time of progression under first line metastatic treatment. A total of 42 patients were included, with a median adjuvant AI exposure of 60 months (range 41-85). No circulating ESR1 mutation was detectable at the end of AI adjuvant therapy. At first relapse, 5.3% of the patients (2/38) had a detectable circulating ESR1 mutation. At time of progression on first-line metastatic treatment, 33% of the patients (7/21) under AI had a detectable circulating ESR1 mutation compared to none of the patients under chemotherapy (0/10). The two patients with a detectable ESR1 mutation at relapse were treated by AI and had an increase of their variant allele fraction at time of progression on first-line metastatic treatment. Circulating ESR1 mutation detection at the end of AI-based adjuvant treatment is not clinically useful. Circulating ESR1 mutation could be assessed as soon as first relapse to guide interventional studies.

Pharmacological Treatment of Pain in Cancer Patients: The Role of Adjuvant Analgesics, a Systematic Review.

PubMed

van den Beuken-van Everdingen, Marieke H J; de Graeff, Alexander; Jongen, Joost L M; Dijkstra, Denise; Mostovaya, Irina; Vissers, Kris C

2017-03-01

In patients with cancer, pain is one of the most feared and burdensome symptoms. Adjuvant analgesics are an important cornerstone on which treatment of pain in patients with cancer is based. To update our guidelines for the treatment of pain in patients with cancer, we performed a systematic review on the use of adjuvant analgesics in pain in cancer. A systematic search of the literature was performed searching for articles that studied the effect of (1) antidepressants, (2) anti-epileptics, (3) N-methyl-d-aspartate (NMDA) receptor antagonists, and (4) other adjuvant analgesics in patients with cancer pain and described their effects on pain intensity and/or side effects. Based on the keywords and after reading the full papers, we could include 12 papers on anticonvulsants, 10 papers on antidepressants, four on NMDA receptor antagonists, and 10 papers on other adjuvant analgesics. The methodological quality of the included papers was graded as low to very low. Overall, there was a low quality of evidence that gabapentin, pregabalin, amitriptyline, and venlafaxine were effective in reducing pain intensity in patients with cancer pain. There was insufficient evidence on the effectiveness of lamotrigine, levetiracetam, NMDA antagonists, cannabinoids, corticosteroids, and local anesthetics on reducing pain intensity in patients with cancer pain. The quality of currently available evidence on the effectiveness of adjuvant analgesics in the treatment of cancer pain is low. The treatment of pain associated with cancer should be tailored to the patient's personal preferences. © 2016 World Institute of Pain.

Treatment of sentence comprehension and production in aphasia: is there cross-modal generalisation?

PubMed

Adelt, Anne; Hanne, Sandra; Stadie, Nicole

2016-09-09

Exploring generalisation following treatment of language deficits in aphasia can provide insights into the functional relation of the cognitive processing systems involved. In the present study, we first review treatment outcomes of interventions targeting sentence processing deficits and, second report a treatment study examining the occurrence of practice effects and generalisation in sentence comprehension and production. In order to explore the potential linkage between processing systems involved in comprehending and producing sentences, we investigated whether improvements generalise within (i.e., uni-modal generalisation in comprehension or in production) and/or across modalities (i.e., cross-modal generalisation from comprehension to production or vice versa). Two individuals with aphasia displaying co-occurring deficits in sentence comprehension and production were trained on complex, non-canonical sentences in both modalities. Two evidence-based treatment protocols were applied in a crossover intervention study with sequence of treatment phases being randomly allocated. Both participants benefited significantly from treatment, leading to uni-modal generalisation in both comprehension and production. However, cross-modal generalisation did not occur. The magnitude of uni-modal generalisation in sentence production was related to participants' sentence comprehension performance prior to treatment. These findings support the assumption of modality-specific sub-systems for sentence comprehension and production, being linked uni-directionally from comprehension to production.

[Music as an adjuvant treatment for anxiety in pediatric oncologic patients].

PubMed

Sepúlveda-Vildósola, Ana Carolina; Herrera-Zaragoza, Octavio René; Jaramillo-Villanueva, Leonel; Anaya-Segura, Armando

2014-01-01

Music has been used as adjuvant therapy for anxiety and it is based on scientific principles. Tone, rhythm, harmony and time are crucial for its efficacy. Chemotherapy treatment frequently produces important stress in pediatric patients. This may delay treatment occasionally. Our objective was to determine if adjuvant therapy with music reduces anxiety in pediatric oncologic patients under ambulatory chemotherapy. Time series design. We included patients from 8 to 16 years of age who received ambulatory intravenous chemotherapy at the Hospital de Pediatría, Centro Médico Nacional Siglo XXI. They received treatment as usual on the first day, and music therapy during the second day of chemotherapy. A visual scale was used to categorize the level of anxiety prior and after treatment on both days. We included 22 patients. All patients experienced both moderate and high levels of anxiety prior to chemotherapy treatment on both days. There was a statistically significant reduction of anxiety on both groups after chemotherapy, but with lower levels of anxiety in the intervention group. There is an additional benefit with the use of music therapy in the reduction of anxiety in pediatric patients who receive ambulatory chemotherapy.

Health-related quality of life during adjuvant treatment for breast cancer among postmenopausal women.

PubMed

Browall, Maria; Ahlberg, Karin; Karlsson, Per; Danielson, Ella; Persson, Lars-Olof; Gaston-Johansson, Fannie

2008-07-01

The purpose of the present study was twofold: first, to describe changes of Health-Related Quality of Life (HRQoL) during the adjuvant treatment among postmenopausal women with breast cancer; second, in the same population to identify the best predictors of Overall Quality of Life (QoL) after treatment, from perceived functioning, symptoms, emotional distress and clinical/demographic variables measured at baseline. The study group was 150 women (> or = 55 years of age) scheduled for adjuvant chemotherapy (CT, n=75) or radiotherapy (RT, n=75). They were examined before (baseline), during and after completing the treatment. Data about QoL, perceived functioning, symptoms and emotional distress were collected with the European Organisation for Research and Treatment of Cancer (EORTC)-QLQ-C30, BR23 and Hospital Anxiety and Depression Scale (HADS) questionnaires. The general finding was that the adjuvant treatments were associated with decrease in overall QoL, physical and role functioning, anxiety and body image, as well as with increase in fatigue, dyspnoea, pain, nausea/vomiting, constipation and systemic therapy side effects measured over time. For women receiving CT, better emotional functioning and less pain at baseline predicted better overall QoL at the end of the treatment. For women receiving RT, better physical and emotional functioning, less breast symptoms and lower tumour stage at baseline predicted better overall QoL at the end of the treatment.

Contribution of Early Detection and Adjuvant Treatments to Breast Cancer Mortality Reduction in Catalonia, Spain

PubMed Central

Vilaprinyo, Ester; Puig, Teresa; Rue, Montserrat

2012-01-01

Background Reductions in breast cancer (BC) mortality in Western countries have been attributed to the use of screening mammography and adjuvant treatments. The goal of this work was to analyze the contributions of both interventions to the decrease in BC mortality between 1975 and 2008 in Catalonia. Methodology/Principal Findings A stochastic model was used to quantify the contribution of each intervention. Age standardized BC mortality rates for calendar years 1975–2008 were estimated in four hypothetical scenarios: 1) Only screening, 2) Only adjuvant treatment, 3) Both interventions, and 4) No intervention. For the 30–69 age group, observed Catalan BC mortality rates per 100,000 women-year rose from 29.4 in 1975 to 38.3 in 1993, and afterwards continuously decreased to 23.2 in 2008. If neither of the two interventions had been used, in 2008 the estimated BC mortality would have been 43.5, which, compared to the observed BC mortality rate, indicates a 46.7% reduction. In 2008 the reduction attributable to screening was 20.4%, to adjuvant treatments was 15.8% and to both interventions 34.1%. Conclusions/Significance Screening and adjuvant treatments similarly contributed to reducing BC mortality in Catalonia. Mathematical models have been useful to assess the impact of interventions addressed to reduce BC mortality that occurred over nearly the same periods. PMID:22272292

Docetaxel as adjuvant and neoadjuvant treatment for patients with breast cancer.

PubMed

Heys, Steven D; Sarkar, Tarun; Hutcheon, Andrew W

2004-10-01

Developments in the role of adjuvant and neoadjuvant chemotherapy for the treatment of patients with breast cancer have focused on the taxes, in particular, docetaxel. This paper discusses the rationale for the introduction of docetaxel into the management of patients following surgery and also its role in those patients with locally-advanced disease, focussing on key clinical trials. The addition of docetaxel to standard adjuvant chemotherapeutic regimens does seem to result in an increased survival in some patients with early-stage disease. In the neoadjuvant setting, the addition of docetaxel to standard regimens does increase pathological response rates, which is a surrogate marker of eventual outcome.

Pathogenesis and treatment modalities of localized scleroderma.

PubMed

Valančienė, Greta; Jasaitienė, Daiva; Valiukevičienė, Skaidra

2010-01-01

Localized scleroderma is a chronic inflammatory disease primarily of the dermis and subcutaneous fat that ultimately leads to a scar-like sclerosis of connective tissue. The disorder manifests as various plaques of different shape and size with signs of skin inflammation, sclerosis, and atrophy. This is a relatively rare inflammatory disease characterized by a chronic course, unknown etiology, and insufficiently clear pathogenesis. Many factors may influence its appearance: trauma, genetic factors, disorders of the immune system or hormone metabolism, viral infections, toxic substances or pharmaceutical agents, neurogenic factors, and Borrelia burgdorferi infection. Various therapeutic modalities are being used for the treatment of localized scleroderma. There is no precise treatment scheme for this disease. A majority of patients can be successfully treated with topical pharmaceutical agents and phototherapy, but some of them with progressive, disseminated, and causing disability localized scleroderma are in need of systemic treatment. The aim of this article is not only to dispute about the clinical and morphological characteristics of localized scleroderma, but also to present the newest generalized data about the possible origin, pathogenesis, and treatment modalities of this disease.

The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma.

PubMed

Trinh, Van Anh; Zobniw, Chrystia; Hwu, Wen-Jen

2017-08-01

Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma. A literature search using PubMed database was undertaken using search words melanoma, interferon-alfa, pegylated interferon-alfa, adjuvant therapy. Expert opinion: Currently, there is no international consensus regarding the optimal dosing schedule for adjuvant IFNα, but HD IFNα-2b remains the most widely used regimen. The AEs of HD IFNα-2b are substantial; however, toxicity management experience amassed over the past 2 decades has significantly improved safety. Many exciting studies are ongoing to examine the roles of immune checkpoint inhibitors and BRAF-targeted therapies in the adjuvant setting and will further delineate the role of adjuvant IFNα.

Adjuvant Maneuvers for Residual Curvature Correction During Penile Prosthesis Implantation in Men with Peyronie's Disease.

PubMed

Berookhim, Boback M; Karpman, Edward; Carrion, Rafael

2015-11-01

The surgical treatment of comorbid erectile dysfunction and Peyronie's disease has long included the implantation of an inflatable penile prosthesis as well as a number of adjuvant maneuvers to address residual curvature after prosthesis placement. To review the various surgical options for addressing curvature after prosthesis placement, with specific attention paid to an original article by Wilson et al. reporting on modeling over a penile prosthesis for the management of Peyronie's disease. A literature review was performed analyzing articles reporting the management of penile curvature in patients undergoing implantation of an inflatable penile prosthesis. Reported improvement in Peyronie's deformity as well as the complication rate associated with the various surgical techniques described. Modeling is a well-established treatment modality among patients with Peyronie's disease undergoing penile prosthesis implantation. A variety of other adjuvant maneuvers to address residual curvature when modeling alone is insufficient has been presented in the literature. Over 20 years of experience with modeling over a penile prosthesis have proven the efficacy and safety of this treatment option, providing the surgeon a simple initial step for the management of residual curvature after penile implantation which allows for the use of additional adjuvant maneuvers in those with significant deformities. © 2015 International Society for Sexual Medicine.

Adjuvant Radiation Therapy Treatment Time Impacts Overall Survival in Gastric Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

McMillan, Matthew T.; Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Ojerholm, Eric

Purpose: Prolonged radiation therapy treatment time (RTT) is associated with worse survival in several tumor types. This study investigated whether delays during adjuvant radiation therapy impact overall survival (OS) in gastric cancer. Methods and Materials: The National Cancer Data Base was queried for patients with resected gastric cancer who received adjuvant radiation therapy with National Comprehensive Cancer Network–recommended doses (45 or 50.4 Gy) between 1998 and 2006. RTT was classified as standard (45 Gy: 33-36 days, 50.4 Gy: 38-41 days) or prolonged (45 Gy: >36 days, 50.4 Gy: >41 days). Cox proportional hazards models evaluated the association between the following factors and OS: RTT, interval from surgery to radiationmore » therapy initiation, interval from surgery to radiation therapy completion, radiation therapy dose, demographic/pathologic and operative factors, and other elements of adjuvant multimodality therapy. Results: Of 1591 patients, RTT was delayed in 732 (46%). Factors associated with prolonged RTT were non-private health insurance (OR 1.3, P=.005) and treatment at non-academic facilities (OR 1.2, P=.045). Median OS and 5-year actuarial survival were significantly worse in patients with prolonged RTT compared with standard RTT (36 vs 51 months, P=.001; 39 vs 47%, P=.005); OS worsened with each cumulative week of delay (P<.0004). On multivariable analysis, prolonged RTT was associated with inferior OS (hazard ratio 1.2, P=.002); the intervals from surgery to radiation therapy initiation or completion were not. Prolonged RTT was particularly detrimental in patients with node positivity, inadequate nodal staging (<15 nodes examined), and those undergoing a cycle of chemotherapy before chemoradiation therapy. Conclusions: Delays during adjuvant radiation therapy appear to negatively impact survival in gastric cancer. Efforts to minimize cumulative interruptions to <7 days should be considered.« less

Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

PubMed

Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

2005-03-01

The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients <40 years of age and with estrogen receptor-positive tumors, ovarian suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

A reformed surgical treatment modality for children with giant cystic craniopharyngioma.

PubMed

Zhu, Wanchun; Li, Xiang; He, Jintao; Sun, Tao; Li, Chunde; Gong, Jian

2017-09-01

Surgical removal plays an important role in treating children's craniopharyngioma. For a safe and minimally invasive craniotomy, a reformed surgical modality was proposed in this paper by combining the insertion of an Ommaya reservoir system (ORS) by stereotactic puncture, aspiration of cystic fluid in 2-day interval for consecutive 7-10 days, and the delayed tumor resection. Eleven patients (aged from 5 to 9 years old) with giant cystic craniopharyngiomas who had undergone the reformed surgical modality during November 2014 and December 2015 were collected as group A. In contrast, seven patients (aged from 5 to 11 years old) who had undergone the traditional directed operation without any prior management from January 2014 to October 2014 were collected into group B. A retrospective analysis was performed for both groups at one institution. The preoperative and postoperative clinical presentations, neuroimaging, early postoperative outcome, and the surgery-related complications of both groups were reviewed. For group A, the mean value of the maximum tumor diameters shank from 52.36 to 23.82 mm after implementing aspiration of the cystic fluid in 1-day interval for consecutive 8.23 days. Eight patients (72.73%) in group A underwent a gross total resection (GTR), while two (28.57%) patients underwent GTR in group B. The postoperative electrolyte disturbance rate and endocrine disorder rate of group B were significantly higher than those of group A (42.86 vs 36.36%; 71.43 vs 45.45%). Postoperative long-term diabetes insipidus only occurred in one patient of group B, and postoperative visual deterioration occurred in two patients of group B. Besides, one patient of group B died of severe postoperative hypothalamus dysfunction. Patients with residual tumors were applied with additional adjuvant radiotherapy, and no recurrence was observed in follow-up examinations. A favorable outcome can be achieved by combining the insertion of an ORS by stereotactic puncture

Current and Under Development Treatment Modalities of Psoriasis: A Review.

PubMed

Albaghdadi, Abdullah

2017-01-01

Psoriasis is a chronic and complex autoimmune inflammatory skin disease that affects over 125 million people worldwide. It can exhibit at any age, in spite of the fact that children are less normally influenced than adults. It is characterized by distinct erythematous plaques shielded with conspicuous silvery scales that shows up in different areas of the skin. Knowledge of pathophysiology, especially the pathogenesis of psoriasis, has significantly progressed in the recent decade. Advancement in molecular knowledge leads to better understanding of the disease, thus influencing the development of efficient treatment modalities. However, even with the availability of various options of treatment most of the efficient treatment modalities are costly. Expenses of health care bring about major financial weight to the patients as well as to health care systems. Thus, it was important to review the available current treatment options and those which are under development, in terms of efficacy, safety and cost to assist in selecting the most appropriate treatment for psoriasis patients. Literatures were searched by using key words psoriasis, topical treatment, systemic treatment, biologics and phototherapies, on Embase, Medline, Jstor, Cochrane and Merck Index databases. Life-style choices such as smoking, alcohol consumption, obesity and stress are recognised as risk factors and triggers associated with psoriasis. Psoriasis poses psycho-social and economic burden on affected patients that sometimes leads to depression, reduced social interaction and suicidal tendencies in patients. Depending on the type, severity and extent of the disease, comorbidities, patient preference, efficacy and safety profile, numerous treatment modalities and therapeutic agents are available such as topical, systemic, biologic and phototherapeutic treatments. However, it was found that among all the current available treatments for psoriasis, biologic agents and phototherapeutic modalities are

Efficacy of aloe vera gel as an adjuvant treatment of oral submucous fibrosis.

PubMed

Alam, Sarwar; Ali, Iqbal; Giri, K Y; Gokkulakrishnan, S; Natu, Subodh S; Faisal, Mohammad; Agarwal, Anshita; Sharma, Himanshu

2013-12-01

Definitive therapy is not defined for the management of oral submucous fibrosis (OSMF). This study evaluated the efficacy of aloe vera gel as an adjuvant treatment of OSMF. A double-blind, placebo-controlled, parallel-group randomized controlled trial was conducted on 60 subjects with OSMF divided into medicinal treatment (submucosal injection of hyaluronidase and dexamethasone, n = 30) and surgical treatment (n = 30) categories. Each category was randomly divided into groups A (with aloe vera, n = 15 per category) and B (without aloe vera, n = 15 per category). Follow-up assessment for various symptoms was performed, and results were analyzed using paired and unpaired Student t tests. The group receiving aloe vera had a significant improvement in most symptoms of OSMF (P < .01) compared with the non-aloe vera group, in both the medicinal and surgical categories. Aloe vera gel was effective as an adjuvant in treatment of OSMF. Copyright © 2013 Elsevier Inc. All rights reserved.

Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA.

PubMed

Thumallapally, Nishitha; Meshref, Ahmed; Mousa, Mohammed; Terjanian, Terenig

2017-01-05

Solitary plasmacytoma (SP) is a localized neoplastic plasma cell disorder with an annual incidence of less than 450 cases. Given the rarity of this disorder, it is difficult to conduct large-scale population studies. Consequently, very limited information on the disorder is available, making it difficult to estimate the incidence and survival rates. Furthermore, limited information is available on the efficacy of various treatment modalities in relation to primary tumor sites. The data for this retrospective study were drawn from the Surveillance, Epidemiology and End Results (SEER) database, which comprises 18 registries; patient demographics, treatment modalities and survival rates were obtained for those diagnosed with SP from 1998 to 2007. Various prognostic factors were analyzed via Kaplan-Meier analysis and log-rank test, with 5-year relative survival rate defined as the primary outcome of interest. Cox regression analysis was employed in the multivariate analysis. The SEER search from 1998 to 2007 yielded records for 1691 SP patients. The median age at diagnosis was 63 years. The patient cohort was 62.4% male, 37.6% female, 80% Caucasian, 14.6% African American and 5.4% other races. Additionally, 57.8% had osseous plasmacytoma, and 31.9% had extraosseous involvement. Unspecified plasmacytoma was noted in 10.2% of patients. The most common treatment modalities were radiotherapy (RT) (48.8%), followed by combination surgery with RT (21.2%) and surgery alone (11.6%). Univariate analysis of prognostic factors revealed that the survival outcomes were better for younger male patients who received RT with surgery (p < 0.05). Additionally, patients who received neoadjuvant RT had increased survival rates compared to those receiving adjuvant RT (86% vs 73%, p < 0.05). Furthermore, the analyses revealed that 5-year survival rates for patients with axial plasmacytoma were superior when RT was combined with surgery (p < 0.05). In the multivariate analysis

Efficacy and safety of azathioprine and dapsone as an adjuvant in the treatment of bullous pemphigoid.

PubMed

Tirado-Sánchez, A; Díaz-Molina, V; Ponce-Olivera, R M

2012-01-01

Bullous pemphigoid is a chronic, blistering and autoimmune disease, common in old age. The treatment usually includes systemic steroids, however, these cause high morbidity rates, and then different products that function as adjuvants have been tried. At present, there are no studies to determine which adjuvant offers a better efficacy and safety profile. We performed a retrospective study which included the records of patients with bullous pemphigoid, treated either with azathioprine or dapsone. We evaluated the time to achieve complete remission, the time to inhibit disease progression, and the control of pruritus. Fifteen records of patients were selected, eight (53%) treated with azathioprine and seven (47%) with dapsone. Complete remission was achieved at week six in both groups. We found no difference in the inhibition of disease progression (p=0.083). Pruritus was controlled at four weeks of treatment in both treatments. Both products are effective as adjuvant in the treatment of bullous pemphigoid, with an acceptable safety profile. Copyright © 2010 SEICAP. Published by Elsevier Espana. All rights reserved.

Adjuvant treatment or primary topical monotherapy for ocular surface squamous neoplasia: a systematic review.

PubMed

Viani, Gustavo Arruda; Fendi, Ligia Issa de

2017-01-01

In this systematic review, we evaluated studies involving adjuvant and primary topical treatment for ocular surface squamous neoplasia (OSSN). The findings were: (i) adjuvant 5-fluorouracil (5-FU) reduces the risk of relapse after surgical excision with mild side effects [level Ib, grade of recommendation (GR) A]. (ii) Primary topical mitomycin (MMC) produces a high rate of complete response, low recurrence rate, and mild side effects (level Ib, GR A). (iii) Primary chemotherapy versus adjuvant chemotherapy produce similar rates of recurrence, with no significant difference (level IIb, GR B). (iv) Adjuvant 5-FU versus MMC showed no significant differences, with mild side effects in both groups and a better toxicity profile for MMC (level III, GR C). (v) Primary topical 5-FU versus MMC versus interferon (IFN) showed similar rates of tumor recurrence, mild side effects for all drugs, and more severe side effects in the 5-FU arm, followed successively by MMC and IFN (level III, GR C).

Dosimetric comparison of different treatment modalities for stereotactic radiotherapy.

PubMed

Hsu, Shih-Ming; Lai, Yuan-Chun; Jeng, Chien-Chung; Tseng, Chia-Ying

2017-09-16

The modalities for performing stereotactic radiotherapy (SRT) on the brain include the cone-based linear accelerator (linac), the flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) linac, and tomotherapy. In this study, the cone-based linac, FFF-VMAT linac, and tomotherapy modalities were evaluated by measuring the differences in doses delivered during brain SRT and experimentally assessing the accuracy of the output radiation doses through clinical measurements. We employed a homemade acrylic dosimetry phantom representing the head, within which a thermoluminescent dosimeter (TLD) and radiochromic EBT3 film were installed. Using the conformity/gradient index (CGI) and Paddick methods, the quality of the doses delivered by the various SRT modalities was evaluated. The quality indicators included the uniformity, conformity, and gradient indices. TLDs and EBT3 films were used to experimentally assess the accuracy of the SRT dose output. The dose homogeneity indices of all the treatment modalities were lower than 1.25. The cone-based linac had the best conformity for all tumors, regardless of the tumor location and size, followed by the FFF-VMAT linac; tomography was the worst-performing treatment modality in this regard. The cone-based linac had the best gradient, regardless of the tumor location and size, whereas the FFF-VMAT linac had a better gradient than tomotherapy for a large tumor diameter (28 mm). The TLD and EBT3 measurements of the dose at the center of tumors indicated that the average difference between the measurements and the calculated dose was generally less than 4%. When the 3% 3-mm gamma passing rate metric was used, the average passing rates of all three treatment modalities exceeded 98%. Regarding the dose, the cone-based linac had the best conformity and steepest dose gradient for tumors of different sizes and distances from the brainstem. The results of this study suggest that SRT should be performed using the cone

Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

PubMed

Gao, Sarah J; Park, Henry S; Corso, Christopher D; Rutter, Charles E; Kim, Anthony W; Johung, Kimberly L

2017-07-01

The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN + disease stratified by margin status. We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base. Patients were categorized as having received surgical resection alone, surgical resection followed by chemotherapy (S+CT), and surgical resection followed by concurrent chemoradiation therapy (S+CRT). Subset analyses were conducted on margin-negative and margin-positive patients. Overall survival was compared by Kaplan-Meier estimation, the log-rank test, and multivariable Cox regression analysis. Among 443 patients, 52.6% received surgical resection alone, 18.7% received S+CT, and 28.6% received S+CRT. Significantly more adenocarcinoma patients received adjuvant treatment (50.8%) than squamous cell carcinoma patients (27.7%, p = 0.001). On multivariable analysis, S+CT (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; p = 0.014) and S+CRT (hazard ratio, 0.73; 95% confidence interval,. 0.55 to 0.98; p = 0.038) both were associated with significantly increased overall survival. These findings persisted among margin-negative patients. However, in margin-positive patients, S+CRT (hazard ratio, 0.29; p = 0.002) was the only treatment arm that was associated with significantly improved survival compared with surgical resection alone. Among cT1-2 N0 pN + esophageal cancer patients, adjuvant chemotherapy may be sufficient for margin-negative patients, whereas adjuvant chemoradiation therapy appears necessary for margin-positive patients. Further prospective studies are needed to confirm the results. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Adjuvant radiation therapy for bladder cancer: A dosimetric comparison of techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumann, Brian C.; Noa, Kate; Wileyto, E. Paul

Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to comparemore » plans for bowel and rectal volumes exposed to 35% (V{sub 35%}), 65% (V{sub 65%}), and 95% (V{sub 95%}) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V{sub 35%} {sub rectum}, V{sub 65%} {sub rectum}, and V{sub 95%} {sub rectum}; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V{sub 95%} {sub bowel}, V{sub 65%} {sub bowel}, or V{sub 35%} {sub bowel}). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V{sub 65%} {sub bowel} and V{sub 95%} {sub bowel} for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant

Factors Predictive of Receiving Adjuvant Radiotherapy in High-Intermediate-Risk Stage I Endometrial Cancer.

PubMed

McGunigal, Mary; Pollock, Ariel; Doucette, John T; Liu, Jerry; Chadha, Manjeet; Kalir, Tamara; Gupta, Vishal

2018-06-01

Randomized trials have shown a local control benefit with adjuvant radiotherapy (RT) in high-intermediate-risk endometrial cancer patients, although not all such patients receive RT. We reviewed the National Cancer Data Base to investigate which patient/tumor-related factors are associated with delivery of adjuvant RT. The National Cancer Data Base was queried for patients diagnosed with International Federation of Gynecology and Obstetrics 2009 stage I endometrioid adenocarcinoma from 1998 to 2012 who underwent surgery +/- adjuvant RT. Exclusion criteria were unknown stage/grade, nonsurgical primary therapy, less than 30 days' follow-up, RT of more than 6 months after surgery, or palliative treatment. High-intermediate risk was defined based on Post Operative Radiation Therapy in Endometrial Carcinoma 2 criteria: older than 60 years with stage IA grade 3 or stage IB grade 1-2. Seventeen thousand five hundred twenty-four met inclusion criteria, and the 13,651 patients with complete data were subjected to a multiple logistic regression analysis; 7814 (57.2%) received surgery alone, and 5837 (42.8%) received surgery + RT. Receipt of adjuvant RT was more likely among black women and women with higher income, Northeastern residence, diagnosis after 2010, greater than 50% myometrial invasion, and receipt of adjuvant chemotherapy (P < 0.05). Patients older than 80 years or those undergoing lymph node dissection were less likely to receive adjuvant RT (P < 0.05). Of those treated with RT, 44.0% received external beam therapy, 54.8% received vaginal cuff brachytherapy, and 0.6% received both. Among irradiated women, patients older than 80 years and those with Northeastern residence, treatment at academic facilities, diagnosis after 2004, and lymph node dissection were more likely to undergo brachytherapy over external beam radiation therapy (P < 0.05). Overall use of adjuvant RT was 28.8% between 1998 and 2004, 42.0% between 2005 and 2010, and 43.4% between 2011 and 2012

Histamine type 2 receptor antagonists as adjuvant treatment for resected colorectal cancer.

PubMed

Deva, Sanjeev; Jameson, Michael

2012-08-15

Anecdotal reports of tumour regression with histamine type 2 receptor antagonists (H(2)RAs) have lead to a series of trials with this class of drug as adjuvant therapy to try and improve outcomes in patients with resected colorectal cancers. There was a plausible scientific rationale suggesting merit in this strategy. This included improved immune surveillance (by way of increasing tumour infiltrating lymphocytes), inhibiting the direct proliferative effect of histamine as a growth factor for colorectal cancer and, in the case of cimetidine, inhibiting endothelial expression of E-selectin (a cell adhesion molecule thought to be critical for metastatic spread). To determine if H(2)RAs improve overall survival when used as pre- and/or postoperative therapy in colorectal cancer patients who have had surgical resection with curative intent. We also stratified the results to see if there was an improvement in overall survival in terms of the specific H(2)RA used. Randomised controlled trials were identified using a sensitive search strategy in the following databases: MEDLINE (1964 to present), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2009), EMBASE (1980 to present) and Cancerlit (1983 to present). Criteria for study selection included: patients with colorectal cancer surgically resected with curative intent; H(2)RAs used i) at any dose, ii) for any length of time, iii) with any other treatment modality and iv) in the pre-, peri- or post-operative period. The results were stratified for the H(2)RA used. The literature search retrieved 142 articles. There were six studies included in the final analysis, published from 1995 to 2007, including a total of 1229 patients. All patients were analysed by intention to treat according to their initial allocation. Log hazard ratios and standard errors of treatment effects (on overall survival) were calculated using the Cochrane statistical package RevMan Version 5. Hazard ratios and standard

Treatment of painful diabetic peripheral neuropathy.

PubMed

Rosenberg, Casandra J; Watson, James C

2015-02-01

Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. To discuss current treatment recommendations for painful diabetic peripheral neuropathy. Literature review. Systematic review of the literature discussing treatment of painful diabetic peripheral neuropathy. Existing treatment guidelines were studied and compared. Painful diabetic peripheral neuropathy occurs in about one in six people with diabetes. This condition impairs quality of life and increases healthcare costs. Treatment recommendations exist, but individual patient therapy can require a trial-and-error approach. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. Adequate medication titration and a reasonable trial period should be allowed. The treatment of painful diabetic peripheral neuropathy can be challenging, but effective management can improve patient's quality of life. Painful diabetic peripheral neuropathy impairs quality of life and can be difficult to treat. Many treatment options have adjuvant benefits or side effects which should be considered prior to initiating therapy. Often, a combination of treatment modalities with various mechanisms of action is required for adequate pain control. © The International Society for Prosthetics and Orthotics 2014.

D-cycloserine adjuvant therapy to molindone in the treatment of schizophrenia.

PubMed

Rosse, R B; Fay-McCarthy, M; Kendrick, K; Davis, R E; Deutsch, S I

1996-10-01

This preliminary investigation examined the therapeutic efficacy of two doses of oral D-cycloserine (5 and 15 mg p.o. b.i.d.) administered as an adjuvant to molindone (150 mg p.o. q.d.) in the treatment of schizophrenia. D-Cycloserine is an agonist at the N-methyl-D-aspartate (NMDA) subclass of glutamate receptor complex. An NMDA agonist intervention was studied because of the schizophreniform psychosis precipitated by phencyclidine (PCP), which is a noncompetitive antagonist at the NMDA glutamate receptor. The PCP model of schizophrenia is regarded as the most comprehensive pharmacological model of this disorder. In this preliminary, placebo-controlled, double-blind, parallel-group study, the measures of treatment efficacy were the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms, and Clinical Global Impression Scale. The final scores for each item of the outcome measures employed were based on the consensus of at least two trained raters who were present during each rating interview. In the 13 subjects evaluated, although the D-cycloserine was well tolerated, neither dose seemed to possess adjuvant therapeutic efficacy. However, since another recent report of nine patients with schizophrenia treated for 2 weeks with a slightly higher dose of D-cycloserine (50 mg/day) described significant clinical and neuropsychological improvement, further study of the adjuvant potential of slightly higher doses of D-cycloserine seems warranted. Additionally, there might be a therapeutic window for D-cycloserine dosing, as daily doses of 250 mg have been associated with symptom worsening.

Predictors of treatment with dialysis modalities in observational studies for comparative effectiveness research*

PubMed Central

Kuttykrishnan, Sooraj; Kalantar-Zadeh, Kamyar; Arah, Onyebuchi A.; Cheung, Alfred K.; Brunelli, Steve; Heagerty, Patrick J.; Katz, Ronit; Molnar, Miklos Z.; Nissenson, Allen; Ravel, Vanessa; Streja, Elani; Himmelfarb, Jonathan; Mehrotra, Rajnish

2015-01-01

Background The Institute of Medicine has identified the comparative effectiveness of renal replacement therapies as a kidney-related topic among the top 100 national priorities. Given the importance of ensuring internal and external validity, the goal of this study was to identify potential sources of bias in observational studies that compare outcomes with different dialysis modalities. Methods This observational cohort study used data from the electronic medical records of all patients that started maintenance dialysis in the calendar years 2007–2011 and underwent treatment for at least 60 days in any of the 2217 facilities operated by DaVita Inc. Each patient was assigned one of six dialysis modalities for each 91-day period from the date of first dialysis (thrice weekly in-center hemodialysis (HD), peritoneal dialysis (PD), less-frequent HD, home HD, frequent HD and nocturnal in-center HD). Results Of the 162 644 patients, 18% underwent treatment with a modality other than HD for at least one 91-day period. Except for PD, patients started treatment with alternative modalities after variable lengths of treatment with HD; the time until a change in modality was shortest for less-frequent HD (median time = 6 months) and longest for frequent HD (median time = 15 months). Between 30 and 78% of patients transferred to another dialysis facility prior to change in modality. Finally, there were significant differences in baseline and time-varying clinical characteristics associated with dialysis modality. Conclusions This analysis identified numerous potential sources of bias in studies of the comparative effectiveness of dialysis modalities. PMID:25883196

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

PubMed Central

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Weight changes after adjuvant treatment in Korean women with early breast cancer.

PubMed

Han, Hye-Suk; Lee, Keun-Wook; Kim, Jee Hyun; Kim, Sung-Won; Kim, In-Ah; Oh, Do-Youn; Im, Seock-Ah; Bang, Soo-Mee; Lee, Jong Seok

2009-03-01

Weight gain is a common problem in breast cancer patients and is reported to be associated with poorer survival. However, most data are limited to Western women. We evaluated weight changes after adjuvant treatment in Korean women with early breast cancer. The authors reviewed the records of 260 patients with stage I-III breast cancer treated between June 2003 and February 2006. Body weight, body mass index (BMI) and menopausal status at baseline and after 3, 6, 12 and 24 months of adjuvant treatment were reviewed. Mean patient age was 47.0 years and 61.1% of women were premenopausal. Among them, 195 patients (75.8%) received chemotherapy and 186 (71.5%) received hormonal therapy. Mean baseline weight was 57.5 +/- 9.8 kg and mean BMI was 23.5 +/- 1.6 kg/m(2) (22.8 +/- 3.0 vs. 24.7 +/- 3.2 kg/m(2) for pre- vs. post-menopausal women, P = 0.286). Mean weight changes were; 0.30 kg at 3 months (P = 0.019); 0.16 kg at 6 months (P = 0.367); -0.34 kg at 1 year (P = 0.082); -0.40 kg at 2 years (P = 0.097). Twenty-three patients (10.4%) gained more than 5% of baseline body weight at 1 year, but no clinical variable was found to be associated with these weight gains. This study shows that Korean women with early breast cancer do not gain weight after adjuvant treatment. Further studies are needed to determine differences between Asian and Western women in terms of weight changes and prognosis in early breast cancer.

Adjuvant treatment with crude rhubarb for patients with acute organophosphorus pesticide poisoning: A meta-analysis of randomized controlled trials.

PubMed

Wang, Lina; Pan, Shuming

2015-12-01

Crude rhubarb has been used to treat critically ill patients for many years. However, no previous meta-analysis has been investigated the benefits of crude rhubarb in patients with acute organophosphorus pesticide poisoning (AOPP). To summarize the beneficial effects of adjuvant treatment with crude rhubarb in patients with AOPP by conducting a meta-analysis. A literature search of the databases through Pubmed, EMBASE, China National Knowledge Infrastructure, VIP, and Wanfang were performed for studies published up to October 2014. Randomized controlled trials (RCTs) investigating the effects of crude rhubarb as adjuvant treatment for patients with AOPP were included. A total of 12 RCTs with 886 patients were identified. Adjuvant treatment with crude rhubarb was associated with a significantly lower incidence of intermediate syndrome (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.10-0.48), as well as multiple organ dysfunction syndrome (RR 0.34; 95% CI 0.20-0.56). Crude rhubarb as adjuvant treatment reduced the total dose of pralidoxime (mean difference [MD] -5.12 g; 95% CI -8.24 to -2.00) or atropine (MD -94.89 mg; 95% CI -156.22 to -33.57), and hospital length of stay (MD -2.79 days; 95% CI -4.19 to -1.39) compared with the controls. This meta-analysis suggests that crude rhubarb as adjuvant treatment appears to have additional beneficial effects in patients with AOPP. More well-designed trials are needed to confirm our findings due to the methodological flaws of the included trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

PubMed Central

Lee, Hyung-Sik; Choi, Youngmin; Hur, Won-Joo; Kim, Hyo-Jin; Kwon, Hyuk-Chan; Kim, Sung-Hyun; Kim, Jae-Seok; Lee, Jong-Hoon; Jung, Ghap-Joong; Kim, Min-Chan

2006-01-01

AIM: To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS: Thirty-one patients who had underwent a potentially curative resection for Stage III and IV (M0) gastric cancer were enrolled. Therapy consists of one cycle of FP (continuous infusion of 5-FU 1000 mg/m2 on d 1 to 5 and cisplatin 60 mg/m2 on d 1) followed by 4500 cGy (180 cGy/d) with capecitabine (1650 mg/m2 daily throughout radiotherapy). Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS: The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients (12.9%) showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION: These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INT-0116. This treatment modality allowed successful loco-regional control rate and 3-year overall survival. PMID:16489675

Predictors of treatment with dialysis modalities in observational studies for comparative effectiveness research.

PubMed

Kuttykrishnan, Sooraj; Kalantar-Zadeh, Kamyar; Arah, Onyebuchi A; Cheung, Alfred K; Brunelli, Steve; Heagerty, Patrick J; Katz, Ronit; Molnar, Miklos Z; Nissenson, Allen; Ravel, Vanessa; Streja, Elani; Himmelfarb, Jonathan; Mehrotra, Rajnish

2015-07-01

The Institute of Medicine has identified the comparative effectiveness of renal replacement therapies as a kidney-related topic among the top 100 national priorities. Given the importance of ensuring internal and external validity, the goal of this study was to identify potential sources of bias in observational studies that compare outcomes with different dialysis modalities. This observational cohort study used data from the electronic medical records of all patients that started maintenance dialysis in the calendar years 2007-2011 and underwent treatment for at least 60 days in any of the 2217 facilities operated by DaVita Inc. Each patient was assigned one of six dialysis modalities for each 91-day period from the date of first dialysis (thrice weekly in-center hemodialysis (HD), peritoneal dialysis (PD), less-frequent HD, home HD, frequent HD and nocturnal in-center HD). Of the 162 644 patients, 18% underwent treatment with a modality other than HD for at least one 91-day period. Except for PD, patients started treatment with alternative modalities after variable lengths of treatment with HD; the time until a change in modality was shortest for less-frequent HD (median time = 6 months) and longest for frequent HD (median time = 15 months). Between 30 and 78% of patients transferred to another dialysis facility prior to change in modality. Finally, there were significant differences in baseline and time-varying clinical characteristics associated with dialysis modality. This analysis identified numerous potential sources of bias in studies of the comparative effectiveness of dialysis modalities. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

PubMed

Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

2017-06-01

This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

Combined-modality treatment for advanced oral tongue squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, K.-H.; Lin, C.-Y.; Kang, C.-J.

Purpose: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). Methods and Materials: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapymore » or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. Results: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. Conclusions: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.« less

Comparison of doxorubicin-cyclophosphamide with doxorubicin-dacarbazine for the adjuvant treatment of canine hemangiosarcoma.

PubMed

Finotello, R; Stefanello, D; Zini, E; Marconato, L

2017-03-01

Canine hemangiosarcoma (HSA) is a neoplasm of vascular endothelial origin that has an aggressive biological behaviour, with less than 10% of dogs alive at 12-months postdiagnosis. Treatment of choice consists of surgery followed by adjuvant doxorubicin-based chemotherapy. We prospectively compared adjuvant doxorubicin and dacarbazine (ADTIC) to a traditional doxorubicin and cyclophosphamide (AC) treatment, aiming at determining safety and assessing whether this regimen prolongs survival and time to metastasis (TTM). Twenty-seven dogs were enrolled; following staging work-up, 18 were treated with AC and 9 with ADTIC. Median TTM and survival time were longer for dogs treated with ADTIC compared with those receiving AC (>550 versus 112 days, P = 0.021 and >550 versus 142 days, P = 0.011, respectively). Both protocols were well tolerated, without need for dose reduction or increased interval between treatments. A protocol consisting of combined doxorubicin and dacarbazine is safe in dogs with HSA and prolongs TTM and survival time. © 2015 John Wiley & Sons Ltd.

The use of strontium-90 Beta radiotherapy as adjuvant treatment for conjunctival melanoma.

PubMed

Cohen, Victoria M L; Papastefanou, Vasilios P; Liu, S; Stoker, Ian; Hungerford, John L

2013-01-01

Background/Aims. To report the safety and efficacy of strontium (Sr(90)) beta radiotherapy as adjuvant treatment for conjunctival melanoma. Methods. A retrospective cohort study was undertaken from 1999 to 2007 of all patients who underwent Sr(90) beta radiotherapy for incompletely excised conjunctival melanoma. Failure of treatment was defined as recurrence of a conjunctival melanoma at the same location following beta radiotherapy. Results. Twenty patients underwent Sr(90) beta radiotherapy for incompletely excised conjunctival melanoma. Median follow-up interval was 59 months (8-152). All patients had conjunctival melanoma involving the bulbar conjunctiva. Underlying diagnoses included PAM with atypia in 60% (12 of 20), PAM without atypia in 15% (3 of 20), and de novo conjunctival melanoma in 25% (5 of 20). Following Sr(90) beta radiotherapy, in 90% (18 out of 20) local control was achieved and visual acuity was not affected in any patient. Three patients (15%) had dry eye symptoms, episcleritis, and descemetcoele, respectively. No cataract or secondary glaucoma was reported. Conclusions. Sr(90) treatment is a very effective adjuvant treatment after excisional biopsy and cryotherapy for conjunctival melanoma with a local success rate of 90%. The treatment is not associated with significant side effects and visual acuity is not affected.

The Use of Strontium-90 Beta Radiotherapy as Adjuvant Treatment for Conjunctival Melanoma

PubMed Central

Cohen, Victoria M. L.; Papastefanou, Vasilios P.; Liu, S.; Stoker, Ian; Hungerford, John L.

2013-01-01

Background/Aims. To report the safety and efficacy of strontium (Sr90) beta radiotherapy as adjuvant treatment for conjunctival melanoma. Methods. A retrospective cohort study was undertaken from 1999 to 2007 of all patients who underwent Sr90 beta radiotherapy for incompletely excised conjunctival melanoma. Failure of treatment was defined as recurrence of a conjunctival melanoma at the same location following beta radiotherapy. Results. Twenty patients underwent Sr90 beta radiotherapy for incompletely excised conjunctival melanoma. Median follow-up interval was 59 months (8–152). All patients had conjunctival melanoma involving the bulbar conjunctiva. Underlying diagnoses included PAM with atypia in 60% (12 of 20), PAM without atypia in 15% (3 of 20), and de novo conjunctival melanoma in 25% (5 of 20). Following Sr90 beta radiotherapy, in 90% (18 out of 20) local control was achieved and visual acuity was not affected in any patient. Three patients (15%) had dry eye symptoms, episcleritis, and descemetcoele, respectively. No cataract or secondary glaucoma was reported. Conclusions. Sr90 treatment is a very effective adjuvant treatment after excisional biopsy and cryotherapy for conjunctival melanoma with a local success rate of 90%. The treatment is not associated with significant side effects and visual acuity is not affected. PMID:23431299

Optimizing Local Control in High‐Grade Uterine Sarcoma: Adjuvant Vaginal Vault Brachytherapy as Part of a Multimodal Treatment

PubMed Central

Annede, Pierre; Gouy, Sébastien; Mazeron, Renaud; Bentivegna, Enrica; Maroun, Pierre; Petit, Claire; Dumas, Isabelle; Leary, Alexandra; Genestie, Catherine; Lhommé, Catherine; Deutsch, Eric; Morice, Philippe; Pautier, Patricia; Haie‐Meder, Christine

2017-01-01

Abstract Purpose. The phase III European Organization for Research and Treatment of Cancer 55874 study has shown that external beam radiotherapy (EBRT) given as adjuvant treatment decreased locoregional recurrences from 40% to 20% in patients (pts) with localized uterine sarcomas (US). No data exist, however, on the place of brachytherapy (BT). Material and Methods. We conducted a single‐center retrospective analysis of pts receiving adjuvant BT of the vaginal vault based on the vaginal mold technique as part of their multimodal adjuvant treatment for a high‐grade US from 1985 to 2015. Treatment characteristics, patterns of relapse, and toxicity were examined. Results. Median follow‐up time was 5.5 years. A total of 98 pts with high‐grade US were identified: 81 leiomyosarcomas and 17 undifferentiated sarcomas. Postoperative chemotherapy was delivered in 53 pts. Median dose of EBRT was 45 Gy in 25 fractions. High‐dose rate, low‐dose rate, and pulsed‐dose rate techniques were used in 66, 31, and 1 pts, respectively. At last follow‐up, six pts (6.1%) experienced a locoregional relapse as first event. The International Federation of Gynecology and Obstetrics stage and the tumor size were associated with a higher probability of local relapse. When focusing on pts with stage I‐III disease, 5‐year overall survival was 77% (95% confidence interval: 67%–87%) and 5‐year survival without locoregional failure was 91% (83%–98%). Toxicities were mild to moderate, with only four acute grade 3 toxicities and two grade 3 late effects. Conclusion. Vaginal vault BT as part of a multimodal adjuvant treatment was associated with a high locoregional control rate and with acceptable side effects in localized high‐grade US. Implications for Practice. This study suggests that an aggressive adjuvant treatment combining chemotherapy and pelvic external beam radiotherapy followed with a brachytherapy of the vaginal vault is associated with a high locoregional

Comparative analysis of success of psoriasis treatment with standard therapeutic modalities and balneotherapy.

PubMed

Baros, Duka Ninković; Gajanin, Vesna S; Gajanin, Radoslav B; Zrnić, Bogdan

2014-01-01

Psoriasis is a chronic, inflammatory, immune-mediated skin disease. In addition to standard therapeutic modalities (antibiotics, cytostatics, phototherapy, photochemotherapy and retinoids), nonstandard methods can be used in the treatment of psoriasis. This includes balneotherapy which is most commonly used in combination with therapeutic resources. The aim of this research was to determine the length of remission of psoriasis in patients treated with standard therapeutic modalities, balneotherapy, and combined treatment (standard therapeutic modalities and balneotherapy). The study analyzed 60 adult patients, of both sexes, with different clinical forms of psoriasis, who were divided into three groups according to the applied therapeutic modalities: the first group (treated with standard therapeutic modalities), the second group (treated with balneotherapy) and the third group (treated with combined therapy-standard methods therapy and balneotherapy). The Psoriasis Area and Severity Index was determined in first, third and sixth week of treatment for all patients. The following laboratory analysis were performed and monitored: C reactive protein, iron with total iron binding capacity, unsaturated iron binding capacity and ferritin, uric acid, rheumatoid factors and antibodies to streptolysin O in the first and sixth week of treatment. The average length of remission in patients treated with standard therapeutic modalities and in those treated with balneotherapy was 1.77 +/- 0.951 months and 1.79 +/- 0.918 months, respectively. There was a statistically significant difference in the duration of remission between the patients treated with combination therapy and patients treated with standard therapeutic modalities (p = 0.019) and balneotherapy (p = 0.032). The best results have been achieved when the combination therapy was administered.

Effect of adjuvant on pendimethalin and dimethenamid-P behaviour in soil.

PubMed

Kočárek, Martin; Kodešová, Radka; Sharipov, Umrbek; Jursík, Miroslav

2018-04-30

Adjuvants are used to improve pesticides' performance. It is expected that adjuvants should increase sorption and persistence, as well as decrease mobility of pesticides in soils. Impact of the "Grounded" brand adjuvant on the behaviour of two herbicides, pendimethalin and dimethenamid-P, was investigated in a Haplic Chernozem. Both herbicides were tested in a laboratory batch sorption experiment with and without adjuvant. The sorption experiment showed that adjuvant negligibly increased dimethenamid-P sorption (K F  = 2.12 and 2.15 cm 3/n  μg 1 - 1/n  g -1 ) but significantly increased pendimethalin sorption (K F  = 270.1 and 3096.4 cm 3/n  μg 1 - 1/n  g -1 ). In field conditions, both herbicides were retained mainly in the topsoil layer (0-5 cm). The pendimethalin dissipation half-lives were similar for all treatments (ranging from 43.0 to 44.6 days) and were not influenced by either irrigation (p = 0.86) or adjuvant (p = 0.9). The dimethenamid-P dissipation half-lives ranged from 8.8 days for irrigated treatment without adjuvant to 12.9 days for non-irrigated treatment with adjuvant. Dimethenamid-P dissipation half-life in treatments with adjuvant was significantly longer (p = 0.049) than was half-life in a treatment without adjuvant. Significantly longer dissipation half-life was observed also in non-irrigated treatments than in irrigated treatments (p = 0.044). Copyright © 2018 Elsevier B.V. All rights reserved.

Different treatment modalities of fusiform basilar trunk aneurysm: study on computational hemodynamics.

PubMed

Wu, Chen; Xu, Bai-Nan; Sun, Zheng-Hui; Wang, Fu-Yu; Liu, Lei; Zhang, Xiao-Jun; Zhou, Ding-Biao

2012-01-01

Unclippable fusiform basilar trunk aneurysm is a formidable condition for surgical treatment. The aim of this study was to establish a computational model and to investigate the hemodynamic characteristics in a fusiform basilar trunk aneurysm. The three-dimensional digital model of a fusiform basilar trunk aneurysm was constructed using MIMICS, ANSYS and CFX software. Different hemodynamic modalities and border conditions were assigned to the model. Thirty points were selected randomly on the wall and within the aneurysm. Wall total pressure (WTP), wall shear stress (WSS), and blood flow velocity of each point were calculated and hemodynamic status was compared between different modalities. The quantitative average values of the 30 points on the wall and within the aneurysm were obtained by computational calculation point by point. The velocity and WSS in modalities A and B were different from those of the remaining 5 modalities; and the WTP in modalities A, E and F were higher than those of the remaining 4 modalities. The digital model of a fusiform basilar artery aneurysm is feasible and reliable. This model could provide some important information to clinical treatment options.

Epirubicin in the adjuvant treatment of splenic hemangiosarcoma in dogs: 59 cases (1997-2004).

PubMed

Kim, Stanley E; Liptak, Julius M; Gall, Trent T; Monteith, Gabrielle J; Woods, J Paul

2007-11-15

To determine the efficacy and toxic effects of epirubicin for the adjuvant treatment of dogs with splenic hemangiosarcoma and identify prognostic factors. Retrospective case series. 59 client-owned dogs that underwent splenectomy for splenic hemangiosarcoma treated with or without epirubicin. Medical records were examined for signalment, clinical signs, diagnostic and surgical findings, and postoperative outcome. For dogs treated with epirubicin, dose numbers, intervals, and reductions and type and severity of toxic effects were recorded. Dogs were allotted to 2 groups: splenectomy alone and splenectomy with adjuvant epirubicin treatment. 18 dogs received epirubicin (30 mg/m(2)) every 3 weeks for up to 4 to 6 treatments. Forty-one dogs were treated with splenectomy alone. The overall median survival time was significantly longer in dogs treated with splenectomy and epirubicin (144 days), compared with splenectomy alone (86 days). Median survival time for dogs with stage I disease (345 days) was significantly longer than for dogs with either stage II (93 days) or III disease (68 days). Seven of 18 dogs treated with epirubicin were hospitalized for signs of adverse gastrointestinal effects. Inappetence, long duration of clinical signs, thrombocytopenia, neutrophilia, and high mitotic rate were negative prognostic factors. Epirubicin may be as efficacious as adjuvant doxorubicin-based protocols, but may result in a higher incidence of adverse gastrointestinal effects. Epirubicin should be considered as an alternative to doxorubicin in dogs with preexisting cardiac disease, as clinical epirubicin cardiotoxicity was not diagnosed in treated dogs.

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs

PubMed Central

Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin CS; Peter, Aniekan I; Azu, Onyemaechi O

2016-01-01

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A–D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility (P < 0.05) and count (P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced (P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant (P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter (P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof. PMID:27818734

Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs.

PubMed

Ogedengbe, Oluwatosin O; Jegede, Ayoola I; Onanuga, Ismail O; Offor, Ugochukwu; Naidu, Edwin Cs; Peter, Aniekan I; Azu, Onyemaechi O

2016-10-01

Increased access to highly active antiretroviral therapy (HAART) has made the management of drug toxicities an increasingly crucial component of HIV. This study investigated the effects of adjuvant use of coconut oil and HAART on testicular morphology and seminal parameters in Sprague- Dawley rats. Twelve adult male Sprague-Dawley rats, weighing 153~169 g were distributed into four groups (A-D) and treated as follows: A served as control (distilled water); B (HAART cocktail- Zidovudine, Lamivudine and Nevirapine); C (HAART + Virgin coconut oil 10 mL/kg) and D (Virgin coconut oil 10 mL/kg). After 56 days of treatment, animals were killed and laparotomy to exercise the epididymis for seminal fluid analyses done whilst testicular tissues were processed for histomorphometric studies. Result showed a significant decline in sperm motility ( P < 0.05) and count ( P < 0.0001) in HAART-treated animals while there was insignificant changes in other parameters in groups C and D except count that was reduced ( P < 0.0001) when compared with controls. Histomorphological studies showed HAART caused disorders in seminiferous tubular architecture with significant ( P < 0.01) decline in epithelial height closely mirrored by extensive reticulin framework and positive PAS cells. Adjuvant Virgin coconut oil + HAART resulted in significant decrease in seminiferous tubular diameter ( P < 0.05), but other morphometric and histological parameters were similar to control or Virgin coconut oil alone (which showed normal histoarchitecture levels). While derangements in testicular and seminal fluid parameters occurred following HAART, adjuvant treatment with Virgin coconut oil restored the distortions emanating thereof.

Outcome of transarterial chemoembolization-based multi-modal treatment in patients with unresectable hepatocellular carcinoma.

PubMed

Song, Do Seon; Nam, Soon Woo; Bae, Si Hyun; Kim, Jin Dong; Jang, Jeong Won; Song, Myeong Jun; Lee, Sung Won; Kim, Hee Yeon; Lee, Young Joon; Chun, Ho Jong; You, Young Kyoung; Choi, Jong Young; Yoon, Seung Kew

2015-02-28

To investigate the efficacy and safety of transarterial chemoembolization (TACE)-based multimodal treatment in patients with large hepatocellular carcinoma (HCC). A total of 146 consecutive patients were included in the analysis, and their medical records and radiological data were reviewed retrospectively. In total, 119 patients received TACE-based multi-modal treatments, and the remaining 27 received conservative management. Overall survival (P<0.001) and objective tumor response (P=0.003) were significantly better in the treatment group than in the conservative group. After subgroup analysis, survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group (P=0.002) but also in the surgical treatment group compared with the loco-regional treatment-only group (P<0.001). Multivariate analysis identified tumor stage (P<0.001) and tumor type (P=0.009) as two independent pre-treatment factors for survival. After adjusting for significant pre-treatment prognostic factors, objective response (P<0.001), surgical treatment (P=0.009), and multi-modal treatment (P=0.002) were identified as independent post-treatment prognostic factors. TACE-based multi-modal treatments were safe and more beneficial than conservative management. Salvage surgery after successful downstaging resulted in long-term survival in patients with large, unresectable HCC.

Outcome of transarterial chemoembolization-based multi-modal treatment in patients with unresectable hepatocellular carcinoma

PubMed Central

Song, Do Seon; Nam, Soon Woo; Bae, Si Hyun; Kim, Jin Dong; Jang, Jeong Won; Song, Myeong Jun; Lee, Sung Won; Kim, Hee Yeon; Lee, Young Joon; Chun, Ho Jong; You, Young Kyoung; Choi, Jong Young; Yoon, Seung Kew

2015-01-01

AIM: To investigate the efficacy and safety of transarterial chemoembolization (TACE)-based multimodal treatment in patients with large hepatocellular carcinoma (HCC). METHODS: A total of 146 consecutive patients were included in the analysis, and their medical records and radiological data were reviewed retrospectively. RESULTS: In total, 119 patients received TACE-based multi-modal treatments, and the remaining 27 received conservative management. Overall survival (P < 0.001) and objective tumor response (P = 0.003) were significantly better in the treatment group than in the conservative group. After subgroup analysis, survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group (P = 0.002) but also in the surgical treatment group compared with the loco-regional treatment-only group (P < 0.001). Multivariate analysis identified tumor stage (P < 0.001) and tumor type (P = 0.009) as two independent pre-treatment factors for survival. After adjusting for significant pre-treatment prognostic factors, objective response (P < 0.001), surgical treatment (P = 0.009), and multi-modal treatment (P = 0.002) were identified as independent post-treatment prognostic factors. CONCLUSION: TACE-based multi-modal treatments were safe and more beneficial than conservative management. Salvage surgery after successful downstaging resulted in long-term survival in patients with large, unresectable HCC. PMID:25741147

Critical decision-making in radiotherapy for early stage breast cancer in a neo-adjuvant treatment era.

PubMed

De Felice, Francesca; Osti, Mattia Falchetto; De Sanctis, Vitaliana; Musio, Daniela; Tombolini, Vincenzo

2017-05-01

In breast cancer management, the role of adjuvant radiation therapy (RT) has been the subject of intense controversy over the past several years, due to the improvement in neoadjuvant chemotherapy (NACT) prescription. One of the most controversial questions regarding indication for adjuvant RT is whether or not RT is essential in patients with early stage disease at diagnosis. The value of adjuvant RT remains highly debatable in those patients with clinically negative nodes at the completion of NACT. Areas covered: This review is focused on this gray area and is intended to assist with clinical decision-making. We provide a comprehensive review using PubMed and meeting proceedings of San Antonio Breast Cancer Symposium, European Society for Radiotherapy & Oncology, European Society of Medical Oncology and American Society of Clinical Oncology. Expert commentary: The identification of potential prognostic factors may lead to novel adjuvant RT indications. Phase III clinical trials are underway and their results will help guide treatment decisions.

Neoadjuvant/adjuvant treatment of high-risk retinoblastoma: a report from the German Retinoblastoma Referral Centre.

PubMed

Künkele, Annette; Wilm, Josephine; Holdt, Markus; Lohmann, Dietmar; Bornfeld, Norbert; Eggert, Angelika; Temming, Petra; Schulte, Johannes H

2015-07-01

Retinoblastoma can extend beyond the structures of the eye, where cells can enter the bloodstream and cause metastases. Various types of protocols for adjuvant treatment risk-adapted according to histopathological risk factors are used worldwide. Between 1997 and 2009, 420 children were diagnosed with retinoblastoma at the German Retinoblastoma Referral Centre and risk factors were assessed. Patients with post-laminar optic nerve infiltration or choroid or minor scleral invasion received six courses of adjuvant chemotherapy using vincristine, etoposide, carboplatin and cyclophosphamide (group 1). Patients with microscopic extension beyond the sclera to the resection margin of the optic nerve or potential spread due to vitrectomy received chemotherapy plus orbital radiotherapy (group 2). Neoadjuvant chemotherapy was performed in patients with local extraocular invasion detected on MRI. Following this protocol, 42 of the 420 patients and 21 referred from other centres showed high-risk histopathological factors qualifying for adjuvant therapy (57 in group 1 and 6 in group 2). Seven of the 63 patients received neoadjuvant and adjuvant treatment. During a mean follow-up of 5.8 (range 0.4-15.4) years, one of six patients in group 2 developed metastases and died. No patients died from toxicity. The 5-year overall survival was 100% for group 1 and 80% for group 2. This retrospective single-site study reveals a 10% incidence of high-risk features in children with retinoblastoma diagnosed at the German Retinoblastoma Referral Centre. Overall survival rates of 98.3% underline the safety of this adjuvant chemotherapy protocol and its efficiency in preventing metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

[Physical treatment modalities for chronic leg ulcers].

PubMed

Dissemond, J

2010-05-01

An increasing numbers of physical treatment options are available for chronic leg ulcer. In this review article, compression therapy, therapeutic ultrasound, negative pressure therapy, extracorporeal shock wave therapy, electrostimulation therapy, electromagnetic therapy, photodynamic therapy, water-filtered infrared-A-radiation and hydrotherapy are discussed in terms of their practical applications and the underlying evidence. With the exception of compression therapy for most of these treatments, good scientific data are not available. However this is a widespread problem in the treatment of chronic wounds. Nevertheless, several of the described methods such as negative pressure therapy represent one of the gold standards in practical treatment of patients with chronic leg ulcers. Although the use of physical treatment modalities may improve healing in patients with chronic leg ulcers, the diagnosis and treatment of the underlying causes are essential for long-lasting success.

Social networking sites: an adjunctive treatment modality for psychological problems.

PubMed

Menon, Indu S; Sharma, Manoj Kumar; Chandra, Prabha S; Thennarasu, K

2014-07-01

Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psychiatry setting of the hospital. Facebook was the most popular sites and used to seek emotional support on the basis of the frequent updates of emotional content that users put in their profile; reconciliations, escape from the problems or to manage the loneliness; getting information about illness and its treatment and interaction with experts and also manifested as problematic use. It has implications for developing social networking based adjunctive treatment modality for psychological problems.

Effectiveness of Psychotherapy in Personality Disorders Not Otherwise Specified: A Comparison of Different Treatment Modalities.

PubMed

Horn, Eva K; Bartak, Anna; Meerman, Anke M M A; Rossum, Bert V; Ziegler, Uli M; Thunnissen, Moniek; Soons, Mirjam; Andrea, Helene; Hamers, Elisabeth F M; Emmelkamp, Paul M G; Stijnen, Theo; Busschbach, Jan J V; Verheul, Roel

2015-01-01

Although personality disorder not otherwise specified (PDNOS) is highly prevalent and associated with a high burden of disease, only a few treatment studies in this patient group exist. This study is the first to investigate the effectiveness of different modalities of psychotherapy in patients with PDNOS, i.e., short-term (up to 6 months) and long-term (more than 6 months) outpatient, day hospital, and inpatient psychotherapy. A total of 205 patients with PDNOS were assigned to one of six treatment modalities. Effectiveness was assessed over 60 months after baseline. The primary outcome measure was symptom severity, and the secondary outcome measures included psychosocial functioning and quality of life. The study design was quasi-experimental, and the multiple propensity score was used to control for initial differences between treatment groups. All treatment modalities showed positive outcomes, especially in terms of improvements of symptom severity and social role functioning. At 12-month follow-up, after adjustment for initial differences between the treatment groups, short-term outpatient psychotherapy and short-term inpatient psychotherapy showed most improvement and generally outperformed the other modalities concerning symptom severity. At 60 months after baseline, effectiveness remained but observed differences between modalities mostly diminished. Patients with PDNOS benefit from psychotherapy both at short-term and long-term follow-up. Short-term outpatient psychotherapy and short-term inpatient psychotherapy seem to be superior to the other treatment modalities at 12-month follow-up. At 60-month follow-up, treatments showed mostly comparable effectiveness. The effectiveness of different modalities of psychotherapy in patients with PDNOS (i.e., short-term vs long-term; outpatient versus day hospital versus inpatient psychotherapy) has not yet been compared. Different modalities of psychotherapy are effective for patients with PDNOS, and positive

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate.

PubMed

Feng, Yan-Ru; Jin, Jing; Ren, Hua; Wang, Xin; Wang, Shu-Lian; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Tang, Yuan; Li, Ning; Liu, Xin-Fan; Fang, Hui; Yu, Zi-Hao; Li, Ye-Xiong

2017-03-09

In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence. In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m 2 ) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included. Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036). In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?

PubMed Central

2011-01-01

Background Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Materials and methods Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: "Endometrial cancer", "Endometrial Neoplasms", "Endometrial Neoplasms/radiotherapy", "External beam radiation therapy", "Brachytherapy" and adequate combinations. Conclusion Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer. PMID:22118369

Survival After Neoadjuvant and Adjuvant Treatments Compared to Surgery Alone for Resectable Esophageal Carcinoma: A Network Meta-analysis.

PubMed

Pasquali, Sandro; Yim, Guang; Vohra, Ravinder S; Mocellin, Simone; Nyanhongo, Donald; Marriott, Paul; Geh, Ju Ian; Griffiths, Ewen A

2017-03-01

This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach. The optimal treatment for resectable esophageal cancer is unknown. A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival. In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87). This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.

Social Networking Sites: An Adjunctive Treatment Modality for Psychological Problems

PubMed Central

Menon, Indu S.; Sharma, Manoj Kumar; Chandra, Prabha S.; Thennarasu, K.

2014-01-01

Background: Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Materials and Methods: Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psychiatry setting of the hospital. Results: Facebook was the most popular sites and used to seek emotional support on the basis of the frequent updates of emotional content that users put in their profile; reconciliations, escape from the problems or to manage the loneliness; getting information about illness and its treatment and interaction with experts and also manifested as problematic use. Conclusions: It has implications for developing social networking based adjunctive treatment modality for psychological problems. PMID:25035548

Effectiveness and Cost-effectiveness of Four Treatment Modalities for Substance Disorders: A Propensity Score Analysis

PubMed Central

Mojtabai, Ramin; Graff Zivin, Joshua

2003-01-01

Objective To assess the effectiveness and cost-effectiveness of four treatment modalities for substance abuse. Data Sources The study used data from the Services Research Outcomes Study (SROS), a survey of 3,047 clients in a random sample of 99 drug treatment facilities across the United States. Detailed sociodemographic, substance use, and clinical data were abstracted from treatment records. Substance abuse outcome and treatment history following discharge from index facilities were assessed using a comprehensive interview with 1,799 of these individuals five years after discharge. Treatment success was defined in two ways: as abstinence and as any reduction in substance use. Study Design Effectiveness and cost-effectiveness of four modalities were compared: inpatient, residential, outpatient detox/methadone, and outpatient drug-free. Clients were stratified based on propensity scores and analyses were conducted within these strata. Sensitivity analyses examined the impact of future substance abuse treatment on effectiveness and cost-effectiveness estimates. Principal Findings Treatment of substance disorders appears to be cost-effective compared to other health interventions. The cost per successfully treated abstinent case in the least costly modality, the outpatient drug-free programs, was $6,300 (95 percent confidence intervals: $5,200–$7,900) in 1990 dollars. There were only minor differences between various modalities of treatment with regard to effectiveness. However, modalities varied considerably with regard to cost-effectiveness. Outpatient drug-free programs were the most cost-effective. There was little evidence that relative effectiveness or cost-effectiveness of programs varied according to factors that were associated with selection into different programs. Conclusions Substance disorders can be treated most cost-effectively in outpatient drug-free settings. Savings from transitioning to the most cost-effective treatment modality may free

Psychosocial influences on suboptimal adjuvant breast cancer treatment adherence among African American women: implications for education and intervention.

PubMed

Magai, Carol; Consedine, Nathan S; Adjei, Brenda A; Hershman, Dawn; Neugut, Alfred

2008-12-01

Despite lower incidence, African American women are at increased risk of dying from breast cancer relative to their European American counterparts. Although there are key differences in both screening behavior and tumor characteristics, an additional part of this mortality difference may lie in the fact that African American women receive suboptimal adjuvant chemotherapy and may receive suboptimal hormonal therapy, therapies that are known to increase survival. The authors consider ethnic differences in the psychosocial factors that have been shown to relate to poor screening adherence and consider how they may influence adherence to breast cancer adjuvant treatment, thus the receipt of suboptimal adjuvant chemo or hormonal therapy. To this end, they review ethnic differences in cognitive, emotional, and social network variables. Psychosocial variables should be included in research designed to understand cancer disparities as well interventions that can be tailored to culturally diverse populations to improve treatment adherence.

Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience.

PubMed

Wolff, Antonio C; Blackford, Amanda L; Visvanathan, Kala; Rugo, Hope S; Moy, Beverly; Goldstein, Lori J; Stockerl-Goldstein, Keith; Neumayer, Leigh; Langbaum, Terry S; Theriault, Richard L; Hughes, Melissa E; Weeks, Jane C; Karp, Judith E

2015-02-01

Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy. © 2014 by American Society of Clinical Oncology.

A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants

PubMed Central

Olschewski, Jessica; Braicu, Ioana; Sehouli, Jalid

2015-01-01

Background. Treatment of borderline ovarian tumors (BOTs) remains contentious, and there is no consensus regarding therapy for BOTs with invasive implants (BOTi). The benefits of platinum-based adjuvant treatment were evaluated in patients with BOTi at primary diagnosis. Methods. The PubMed database was systematically searched for articles using the following terms: ((borderline) OR (low malignant potential) AND (ovarian)) AND ((tumor) OR (cancer)) AND (invasive implants) AND ((follow-up) OR (survival) OR (treatment) OR (chemotherapy) OR (adjuvant treatment) OR (surgery) OR (surgical treatment)). Results. We identified 27 articles including 3,124 patients, 181 with invasive implants. All studies provided information regarding mortality or recurrence rates. Central pathological examination was performed in 19 studies. Eight studies included more than 75% stage I patients; 7 included only advanced-stage patients, and 14 included only serous BOT. The pooled recurrence estimates for both treatment groups (adjuvant treatment: 44.0%, upfront surgery: 21.3%) did not differ significantly (p = .114). A meta-analysis of the 6 studies providing separate mortality data for both treatment groups favored surgical treatment only, but this difference did not reach statistical significance (.05 < p < .1; odds ratio: 0.33; 95% confidence interval: 0.09–1.71; p = .086). We were unable to pool the results of the included studies because not all studies registered events in both treatment groups. Egger’s regression indicated low asymmetry of the studies (p = .39), and no heterogeneity was found (I2 = 0%). Conclusion. We did not find evidence supporting platinum-based adjuvant therapy for BOT with invasive implants. PMID:25601963

Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer.

PubMed

Ribi, K; Aldridge, J; Phillips, K-A; Thompson, A; Harvey, V; Thürlimann, B; Cardoso, F; Pagani, O; Coates, A S; Goldhirsch, A; Price, K N; Gelber, R D; Bernhard, J

2012-05-08

In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low. Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute.

Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base.

PubMed

Cheraghlou, Shayan; Yu, Phoebe K; Otremba, Michael D; Park, Henry S; Bhatia, Aarti; Zogg, Cheryl K; Mehra, Saral; Yarbrough, Wendell G; Judson, Benjamin L

2018-02-15

The growing epidemic of human papillomavirus-positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de-escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base. A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single-modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple-modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy. Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple-modality therapy for patients with stage III disease may improve survival in

Combined modality treatment of aromatherapy, footsoak, and reflexology relieves fatigue in patients with cancer.

PubMed

Kohara, Hiroyuki; Miyauchi, Takako; Suehiro, Yoko; Ueoka, Hiroshi; Takeyama, Hiroyasu; Morita, Tatsuya

2004-12-01

Fatigue is one of the most distressful symptoms experienced by patients with advanced cancer. Aromatherapy, footsoak, and reflexology are popular health care modality treatments in Japan, however, the effectiveness of each treatment for cancer-related fatigue has not been fully established. To investigate the effectiveness of combined modality treatment consisting of aromatherapy, footsoak, and reflexology against fatigue, an open study was performed in 20 terminally ill patients with cancer. After a patch test was performed, patients received aromatherapy that was accompanied with footsoak in warm water containing lavender essential oil for 3 minutes, followed by reflexology treatment with jojoba oil containing lavender for 10 min. Fatigue was evaluated using the Cancer Fatigue Scale (CFS) before, 1 hour after, and 4 hours after treatment. Total CFS scores improved significantly after this treatment (from 25.6 +/- 11.0 to 18.1 +/- 10.0, p < 0.001). Among three CFS subscales, physical and cognitive subscale scores were reduced significantly (11.3 +/- 6.1 to 6.7 +/- 6.1, p < 0.001; 4.5 +/- 3.2 to 2.4 +/- 2.4, p < 0.001). No adverse effects were experienced. Because all patients desired to continue this treatment, they received treatment eight times on average. Combined modality treatment consisting of aromatherapy, footsoak, and reflexology appears to be effective for alleviating fatigue in terminally ill cancer patients. To confirm safety and effectiveness of this combined modality treatment, further investigation including randomized treatment assignment is warranted.

The role of adjuvant treatment in early-stage oral cavity squamous cell carcinoma: An international collaborative study.

PubMed

Fridman, Eran; Na'ara, Shorook; Agarwal, Jaiprakash; Amit, Moran; Bachar, Gideon; Villaret, Andrea Bolzoni; Brandao, Jose; Cernea, Claudio R; Chaturvedi, Pankaj; Clark, Jonathan; Ebrahimi, Ardalan; Fliss, Dan M; Jonnalagadda, Sashikanth; Kohler, Hugo F; Kowalski, Luiz P; Kreppel, Matthias; Liao, Chun-Ta; Patel, Snehal G; Patel, Raj P; Robbins, K Thomas; Shah, Jatin P; Shpitzer, Thomas; Yen, Tzu-Chen; Zöller, Joachim E; Gil, Ziv

2018-05-14

Up to half of patients with oral cavity squamous cell carcinoma (OCSCC) have stage I to II disease. When adequate resection is attained, no further treatment is needed; however, re-resection or radiotherapy may be indicated for patients with positive or close margins. This multicenter study evaluated the outcomes and role of adjuvant treatment in patients with stage I to II OCSCC. Overall survival (OS), disease-specific survival, local-free survival, and disease-free survival rates were calculated with Kaplan-Meier analysis. Of 1257 patients with T1-2N0M0 disease, 33 (2.6%) had positive margins, and 205 (16.3%) had close margins. The 5-year OS rate was 80% for patients with clear margins, 52% for patients with close margins, and 63% for patients with positive margins (P < .0001). In a multivariate analysis, age, depth of invasion, and margins were independent predictors of outcome. Close margins were associated with a >2-fold increase in the risk of recurrence (P < .0001). The multivariate analysis revealed that adjuvant treatment significantly improved the outcomes of patients with close/positive margins (P = .002 to .03). Patients with stage I to II OCSCC and positive/close margins have poor long-term outcomes. For this population, adjuvant treatment may be associated with improved survival. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Update on adjuvant chemotherapy for early breast cancer.

PubMed

Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

2014-01-01

Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come.

Comparison of various treatment modalities for acute tinnitus.

PubMed

Shim, Hyun Joon; Song, Seong Jun; Choi, A Young; Hyung Lee, Rae; Yoon, Sang Won

2011-12-01

Because in most cases the development of tinnitus is triggered by cochlear damage, there exists the opportunity to eliminate tinnitus while the cochlear lesion is still reversible. Therefore, we evaluated the therapeutic effects of various treatment modalities on acute subjective idiopathic tinnitus (SIT) and investigated prognostic factors affecting the treatment outcome. Prospective, controlled, double-blind trial. A total 107 patients who underwent treatment for unilateral SIT that had developed within the previous 3 months completed the study. The patients were randomly assigned into three groups according to the treatment modality: group I (n = 32), alprazolam orally for 3 months; group II (n = 35), as for group I plus four intratympanic dexamethasone (ITD) injections; and group III (n = 40), as for group II plus four intravenous injections of lipo-prostaglandin E(1) . The improvement rate of group II (75.8%) was significantly higher than that of group I (40.3%; P < .05), and there was no significant difference in the improvement rate of group III (50.0%) compared with groups I and II (P > .05). The cure rates of group II (25.8%) and group III (20.0%) were significantly higher than that of group I (9.8%; P < .05). There was a significant correlation between the cure rate and duration of symptoms. The results of the present study indicate that ITD injection plus alprazolam medication is the best treatment choice for acute SIT within 3 months of development. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Nipple-Sparing Mastectomy is Not Associated with a Delay of Adjuvant Treatment.

PubMed

Albright, Emily L; Schroeder, Mary C; Foster, Kendra; Sugg, Sonia L; Erdahl, Lillian M; Weigel, Ronald J; Lizarraga, Ingrid M

2018-07-01

High-volume single-institution studies support the oncologic safety of nipple sparing mastectomy (NSM). Concerns remain regarding the increased potential for complications, recurrence, and delays to subsequent adjuvant therapy. A national database was used to examine treatment and outcomes for NSM patients. Women undergoing unilateral NSM or skin sparing mastectomy (SSM) for stage 0-4 breast cancer from 2004 to 2013 were identified from the National Cancer Database. Demographic and oncologic characteristics, short-term outcomes and time to local and systemic treatment were compared. NSM was performed on 8173 patients: 8.7% were node positive, and for stage 1-4 disease, 10.6% were triple negative (TN) and 15.3% were HER2-positive. NSM patients were less likely than SSM patients to receive chemotherapy [CT] (37.4 vs. 43.4%) or radiation [PMRT] (15.6 vs. 16.9%), and were also more likely to present with clinically early-stage disease. NSM patients with high-risk features were more likely to receive CT in the neoadjuvant [NCT] than adjuvant setting [AC] (OR 3.76, 1.81, and 1.99 for clinical N2/3, TN, and HER2-positive disease, all p < 0.001). On multivariate analysis, NSM patients had a higher rate of pathologic complete response [pCR] (OR 1.41, p < 0.001). Readmission rate, positive margin rate and time to CT, PMRT or hormonal therapy were not increased for NSM compared to SSM patients. Over one third of NSM patients received chemotherapy and/or radiation. NSM patients with high-risk features were more likely to receive NAC and obtain a pCR. NSM patients did not experience worse outcomes or delayed adjuvant therapy compared to SSM.

Influence of adjuvant detached mindfulness and stress management training compared to pharmacologic treatment in primiparae with postpartum depression.

PubMed

Ahmadpanah, Mohammad; Nazaribadie, Marzieh; Aghaei, Elham; Ghaleiha, Ali; Bakhtiari, Azade; Haghighi, Mohammad; Bahmani, Dena Sadeghi; Akhondi, Amineh; Bajoghli, Hafez; Jahangard, Leila; Holsboer-Trachsler, Edith; Brand, Serge

2018-02-01

Ten to 15% of mothers experience postpartum depression (PPD). If untreated, PPD may negatively affect mothers' and infants' mental health in the long term. Accordingly, effective treatments are required. In the present study, we investigated the effect of detached mindfulness (DM) and stress management training (SMT) as adjuvants, compared to pharmacologic treatment only, on symptoms of depression in women with PPD. Forty-five primiparae (mean age: M = 24.5 years) with diagnosed PPD and treated with an SSRI (citalopram; CIT) took part in the study. At baseline, they completed questionnaires covering socio-demographic data and symptoms of depression. Experts rated also symptoms of depression. Next, participants were randomly assigned to one of the following study conditions: adjuvant detached mindfulness (CIT+DM); adjuvant stress management training (CIT+SMT); control condition (CIT). Self- and experts' ratings were completed at the end of the study 8 weeks later, and again at 8 weeks follow-up. Symptoms of depression decreased significantly over time, but more so in the CIT+DM and CIT+SMT group, compared to the control condition. The pattern of results remained stable at follow-up. In primiparae with PPD and treated with a standard SSRI, adjuvant psychotherapeutic interventions led to significant and longer-lasting improvements.

Assessing Instructional Modalities: Individualized Treatment Effects for Personalized Learning

ERIC Educational Resources Information Center

Beemer, Joshua; Spoon, Kelly; Fan, Juanjuan; Stronach, Jeanne; Frazee, James P.; Bohonak, Andrew J.; Levine, Richard A.

2018-01-01

Estimating the efficacy of different instructional modalities, techniques, and interventions is challenging because teaching style covaries with instructor, and the typical student only takes a course once. We introduce the individualized treatment effect (ITE) from analyses of personalized medicine as a means to quantify individual student…

Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

PubMed Central

Eitan, Renana; Lerer, Bernard

2006-01-01

Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT. Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability. PMID:16889109

Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients.

PubMed

Dienstmann, Rodrigo; Salazar, Ramon; Tabernero, Josep

2015-06-01

For more than three decades, postoperative chemotherapy-initially fluoropyrimidines and more recently combinations with oxaliplatin-has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice. © 2015 by American Society of Clinical Oncology.

Adjuvant treatment for resected rectal cancer: impact of standard and intensified postoperative chemotherapy on disease-free survival in patients undergoing preoperative chemoradiation-a propensity score-matched analysis of an observational database.

PubMed

Garlipp, Benjamin; Ptok, Henry; Benedix, Frank; Otto, Ronny; Popp, Felix; Ridwelski, Karsten; Gastinger, Ingo; Benckert, Christoph; Lippert, Hans; Bruns, Christiane

2016-12-01

Adjuvant chemotherapy for resected rectal cancer is widely used. However, studies on adjuvant treatment following neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision (TME) have yielded conflicting results. Recent studies have focused on adding oxaliplatin to both preoperative and postoperative therapy, making it difficult to assess the impact of adjuvant oxaliplatin alone. This study was aimed at determining the impact of (i) any adjuvant treatment and (ii) oxaliplatin-containing adjuvant treatment on disease-free survival in CRT-pretreated, R0-resected rectal cancer patients. Patients undergoing R0 TME following 5-fluorouracil (5FU)-only-based CRT between January 1, 2008, and December 31, 2010, were selected from a nationwide registry. After propensity score matching (PSM), comparison of disease-free survival (DFS) using Kaplan-Meier analysis and log-rank test was performed in (i) patients receiving no vs. any adjuvant treatment and (ii) patients treated with adjuvant 5FU/capecitabine without vs. with oxaliplatin. Out of 1497 patients, 520 matched pairs were generated for analysis of no vs. any adjuvant treatment. Mean DFS was significantly prolonged with adjuvant treatment (81.8 ± 2.06 vs. 70.1 ± 3.02 months, p < 0.001). One hundred forty-eight matched pairs were available for analysis of adjuvant therapy with or without oxaliplatin, showing no improvement in DFS in patients receiving oxaliplatin (76.9 ± 4.12 vs. 79.3 ± 4.44 months, p = 0.254). Local recurrence rate was not significantly different between groups in either analysis. In this cohort of rectal cancer patients treated with neoadjuvant CRT and TME surgery under routine conditions, adjuvant chemotherapy significantly improved DFS. No benefit was observed for the addition of oxaliplatin to adjuvant chemotherapy in this setting.

Current Status of Adjuvant Therapy for Colon Cancer

PubMed Central

André, Thierry; Afchain, Pauline; Barrier, Alain; Blanchard, Pierre; Larsen, Annette K.; Tournigand, Christophe; Louvet, Christophe; de Gramont, Aimery

2007-01-01

Due to its frequency and persistently high mortality, colorectal cancer represents a major public health problem. The use of adjuvant chemotherapy has improved prognosis in stage III disease, but much work remains to be done in optimizing adjuvant treatment, including refinement of ability to predict disease course and response to chemotherapy. The FOLFOX4 regimen is now considered standard treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5-FU) have not proven to be more effective than 5-FU/folinic acid (FA). Oral fluoropyrimidines (eg, capecitabine, UFT + FA) now offer an alternative to intravenous 5-FU. Adjuvant chemotherapy for stage II colorectal cancer is more controversial. Use of adjuvant chemotherapy does not appear to be justified in patients with no particular risk factors (T3N0 with no poor prognosis factor). In contrast, the risk:benefit ratio in patients with one or more poor prognostic factors (T4 tumor, occlusion or perforation, poorly differentiated tumor, vascular invasion, or < 10 lymph nodes examined) appears to favor adjuvant treatment with FOLFOX4. Ongoing adjuvant trials are evaluating bevacizumab and cetuximab combined with 5-FU and oxaliplatin, and are examining the utility of such potential predictive markers as tumor microsatellite instability and loss of heterozygosity. Duration of therapy and prevention of oxaliplatin neurotoxicity are other critical areas for future research. PMID:19262714

Geographic variation in the intended choice of adjuvant treatments for women diagnosed with screen-detected breast cancer in Queensland.

PubMed

Hsieh, Jeff Ching-Fu; Cramb, Susanna M; McGree, James M; Dunn, Nathan A M; Baade, Peter D; Mengersen, Kerrie L

2015-12-02

Although early diagnosis and improved treatment can reduce breast cancer mortality, there still appears to be a geographic differential in patient outcomes. This study aims to determine and quantify spatial inequalities in intended adjuvant (radio-, chemo- and hormonal) therapy usage among women with screen-detected breast cancer in Queensland, Australia. Linked population-based datasets from BreastScreen Queensland and the Queensland Cancer Registry during 1997-2008 for women aged 40-89 years were used. We adopted a Bayesian shared spatial component model to evaluate the relative intended use of each adjuvant therapy across 478 areas as well as common spatial patterns between treatments. Women living closer to a cancer treatment facility were more likely to intend to use adjuvant therapy. This was particularly marked for radiotherapy when travel time to the closest radiation facility was 4 + h (OR =0.41, 95 % CrI: [0.23, 0.74]) compared to <1 h. The shared spatial effect increased towards the centres with concentrations of radiotherapy facilities, in north-east (Townsville) and south-east (Brisbane) regions of Queensland. Moreover, the presence of residual shared spatial effects indicates that there are other unmeasured geographical barriers influencing women's treatment choices. This highlights the need to identify the additional barriers that impact on treatment intentions among women diagnosed with screen-detected breast cancer, particularly for those women living further away from cancer treatment centers.

Orthodontic Treatment Timing and Modalities in Anterior Open Bite: Case Series Study

PubMed Central

Al Hamadi, Wisam; Saleh, Fayez; Kaddouha, Mohamad

2017-01-01

Objective: The purpose of this study was to present early and adult cases of anterior open bite that were treated efficiently using different treatment approaches and mechanics. Materials and Methods: Five patients of different age groups (from 7 to 27 years), suffering from a clear Anterior open bite deformity, were properly diagnosed and relevant treatment modality for each was selected. Results: Positive overbite was efficiently achieved for all patients. Conclusion: Patient compliance is a key factor in using removable habit breakers. However, fixed palatal crib gave the same results but in shorter time. Anterior open bite of skeletal components should be thoroughly evaluated before selecting camouflage or orthognathic surgery treatment modality. PMID:29299074

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: is there a standard of care?

PubMed

Almhanna, Khaldoun; Shridhar, Ravi; Meredith, Kenneth L

2013-04-01

Carcinoma of the esophagus is an aggressive and lethal disease with an increasing incidence worldwide. Despite changes in the treatment approach over the past two decades and even following complete resection, most patients will eventually relapse and die as a result of their disease. Several clinical trials evaluated different modalities in treating locally advanced esophageal cancer; however, because of stage migration and the changes in disease epidemiology, applying these trials to clinical practice has become a daunting task. We searched Medline and conference abstracts for randomized studies published in the past three decades. We restricted our search to articles published in English. Neoadjuvant chemoradiotherapy followed by surgical resection is an accepted standard of care in the United States for patients with locally advanced esophageal cancer. Esophagectomy remains an essential component of treatment and can lead to improved overall survival, especially when performed at high-volume institutions. The role of adjuvant chemotherapy following curative resection in patients who underwent neoadjuvant chemotherapy and radiation remains unclear. Several questions still need to be answered regarding the use of neoadjuvant or adjuvant therapy for patients with resectable esophageal cancer. The optimal chemotherapy regimen has not yet been identified for these patients, although newer therapies show promise.

Improved Survival Endpoints With Adjuvant Radiation Treatment in Patients With High-Risk Early-Stage Endometrial Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elshaikh, Mohamed A., E-mail: melshai1@hfhs.org; Vance, Sean; Suri, Jaipreet S.

2014-02-01

Purpose/Objective(s): To determine the impact of adjuvant radiation treatment (RT) on recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) in patients with high-risk 2009 International Federation of Gynecology and Obstetrics stage I-II endometrial carcinoma. Methods and Materials: We identified 382 patients with high-risk EC who underwent hysterectomy. RFS, DSS, and OS were calculated from the date of hysterectomy by use of the Kaplan-Meier method. Cox regression modeling was used to explore the risks associated with various factors on survival endpoints. Results: The median follow-up time for the study cohort was 5.4 years. The median age was 71 years.more » All patients underwent hysterectomy and salpingo-oophorectomy, 93% had peritoneal cytology, and 85% underwent lymphadenectomy. Patients with endometrioid histology constituted 72% of the study cohort, serous in 16%, clear cell in 7%, and mixed histology in 4%. Twenty-three percent of patients had stage II disease. Adjuvant management included RT alone in 220 patients (57%), chemotherapy alone in 25 patients (7%), and chemoradiation therapy in 27 patients (7%); 110 patients (29%) were treated with close surveillance. The 5-year RFS, DSS, and OS were 76%, 88%, and 73%, respectively. On multivariate analysis, adjuvant RT was a significant predictor of RFS (P<.001) DSS (P<.001), and OS (P=.017). Lymphovascular space involvement was a significant predictor of RFS and DSS (P<.001). High tumor grade was a significant predictor for RFS (P=.038) and DSS (P=.025). Involvement of the lower uterine segment was also a predictor of RFS (P=.049). Age at diagnosis and lymphovascular space involvement were significant predictors of OS: P<.001 and P=.002, respectively. Conclusion: In the treatment of patients with high-risk features, our study suggests that adjuvant RT significantly improves recurrence-free, disease-specific, and overall survival in patients with early-stage endometrial

Shared decision-making - Rhetoric and reality: Women's experiences and perceptions of adjuvant treatment decision-making for breast cancer.

PubMed

Mahmoodi, Neda; Sargeant, Sally

2017-01-01

This interview-based study uses phenomenology as a theoretical framework and thematic analysis to challenge existing explanatory frameworks of shared decision-making, in an exploration of women's experiences and perceptions of shared decision-making for adjuvant treatment in breast cancer. Three themes emerged are as follows: (1) women's desire to participate in shared decision-making, (2) the degree to which shared decision-making is perceived to be shared and (3) to what extent are women empowered within shared decision-making. Studying breast cancer patients' subjective experiences of adjuvant treatment decision-making provides a broader perspective on patient participatory role preferences and doctor-patient power dynamics within shared decision-making for breast cancer.

Physician perceptions of the value of physical modalities in the treatment of musculoskeletal disease.

PubMed

Rush, P J; Shore, A

1994-06-01

We randomly surveyed 100 specialists in rehabilitation medicine and 100 rheumatologists concerning their perceptions of the value of 11 different physical modalities--cold, active and passive exercise, interferential current, laser, magnetotherapy, microwave, shortwave diathermy, traction, ultrasound and transcutaneous nerve stimulation in the treatment of seven different musculoskeletal conditions--acute arthritis, joint contracture, neck pain, back pain, tendinitis, reflex sympathetic dystrophy and frozen shoulder. There were significant differences in the perceived benefits of modalities which varied by modality and condition. Overall, rehabilitation medicine specialists regarded modalities to be helpful more often than rheumatologists (P < 0.001).

Tolerance of adjuvant letrozole outside of clinical trials.

PubMed

Fontaine, C; Meulemans, A; Huizing, M; Collen, C; Kaufman, L; De Mey, J; Bourgain, C; Verfaillie, G; Lamote, J; Sacre, R; Schallier, D; Neyns, B; Vermorken, J; De Grève, J

2008-08-01

Recently aromatase inhibitors have become a standard care as an adjuvant treatment for many postmenopausal patients with hormone receptor positive early breast cancer. Adjuvant letrozole was made available either immediately postoperative, after 2-3 years of tamoxifen, or as an extended treatment after 5 years of tamoxifen. Between October 2003 and October 2005, we analyzed the subjective tolerance in 185 postoperative early breast cancer patients receiving letrozole outside of a clinical trial. The most prominent toxicity was musculoskeletal pain. In addition hot flushes, increased fatigue, nausea, vomiting, anorexia, mood disturbances, vaginal dryness, hair loss and rash were also recorded. In contrast to the prospective randomized clinical trials, a high drop-out rate of 20% was documented, mainly due to aromatase inhibitor-associated arthralgia syndrome interfering significantly with the daily life of our patients. Although adjuvant aromatase inhibitors have proven to be generally superior to tamoxifen in the adjuvant setting, it is important to focus attention on the tolerance during the adjuvant therapy and to balance this against the potential benefit in individual patients. Alternative options including switching to tamoxifen remain available.

Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sher, David J., E-mail: dsher@lroc.harvard.edu; Thotakura, Vijaya; Balboni, Tracy A.

2011-11-15

Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distributionmore » of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

PubMed

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

PubMed

Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

2012-03-14

Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

Elderly patients with colorectal cancer: treatment modalities and survival in France. National data from the ThInDiT cohort study.

PubMed

Doat, S; Thiébaut, A; Samson, S; Ricordeau, P; Guillemot, D; Mitry, E

2014-05-01

Few data exist on how elderly patients with colorectal cancer (CRC) are actually treated in real-life practice. Based on a national cohort, we analysed routine treatment modalities of the elderly who were diagnosed with CRC in France in 2009. The characteristics of patients and tumours and the cancer treatments received during the first year of all national incident cases of CRC diagnosed between 1st April and 31st December 2009, were compared between a 'younger group' (YG), under 75 years of age (N = 18,410 patients), and an 'older group' (OG), aged 75 and over (N = 13,255 patients). In the OG with metastases at baseline, we analysed two-year overall survival (OS) according to the treatment received (e.g. chemotherapy, surgery) and well-known prognostic factors. Among patients with localised CRC (N = 25,353), surgery was equally performed in both groups in more than 80% of the cases (p=0.52); time to surgery was shorter in the OG (8 versus 23 days) because there was more emergency surgery for occlusion among the OG. Adjuvant chemotherapy was performed in 15% of the OG (versus 29% in the YG) and consisted of 5-fluorouracil (5FU) monotherapy in more than 50% of OG patients. Among patients with metastatic CRC (N = 6,312), palliative chemotherapy was given to 48% of the OG versus 85% of the YG. Chemotherapy regimens included 30% monotherapy with 5FU, 30% oxaliplatin combination and 20% bevacizumab combination in the OG; compared to 10%, 34% and 35%, respectively, in the YG. The median OS for the OG was 8.4 months (versus 22.3 months in the YG) and 17.1 months among elderly patients who received chemotherapy. CRC is more frequently complicated at diagnosis among elderly patients. Adjuvant and palliative chemotherapy is less frequently prescribed among elderly patients. This could be explained by the fact that unfit elderly patients do not deserve chemotherapy, but certainly also reflect the fact that some fit elderly patients are undertreated. Copyright © 2014

Activity of glycated chitosan and other adjuvants to PDT vaccines

NASA Astrophysics Data System (ADS)

Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

2015-03-01

Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

A Comparison of Therapeutic Factors in Two Group Treatment Modalities: Verbal and Art Therapy.

ERIC Educational Resources Information Center

Shechtman, Zipora; Perl-Dekel, Ofra

2000-01-01

Compares therapeutic factors in verbal and art group psychotherapy in a psychiatric day-treatment clinic in Israel. Results only partly support the differences between modalities, but do reveal significant differences between participants with only a few interactions between participants and modalities. All therapeutic factors appear in both…

Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

PubMed Central

Bai, Litao; Gao, Jialiang; Wei, Fan; Zhao, Jing; Wang, Danwei; Wei, Junping

2018-01-01

Ginseng, one of the oldest traditional Chinese medicinal herbs, has been used widely in China and Asia for thousands of years. Ginsenosides extracted from ginseng, which is derived from the roots and rhizomes of Panax ginseng C. A. Meyer, have been used in China as an adjuvant in the treatment of diabetes mellitus. Owing to the technical complexity of ginsenoside production, the total ginsenosides are generally extracted. Accumulating evidence has shown that ginsenosides exert antidiabetic effects. In vivo and in vitro tests revealed the potential of ginsenoside Rg1, Rg3, Rg5, Rb1, Rb2, Rb3, compound K, Rk1, Re, ginseng total saponins, malonyl ginsenosides, Rd, Rh2, F2, protopanaxadiol (PPD) and protopanaxatriol (PPT)-type saponins to treat diabetes and its complications, including type 1 diabetes mellitus, type 2 diabetes mellitus, diabetic nephropathy, diabetic cognitive dysfunction, type 2 diabetes mellitus with fatty liver disease, diabetic cerebral infarction, diabetic cardiomyopathy, and diabetic erectile dysfunction. Many effects are attributed to ginsenosides, including gluconeogenesis reduction, improvement of insulin resistance, glucose transport, insulinotropic action, islet cell protection, hepatoprotective activity, anti-inflammatory effect, myocardial protection, lipid regulation, improvement of glucose tolerance, antioxidation, improvement of erectile dysfunction, regulation of gut flora metabolism, neuroprotection, anti-angiopathy, anti-neurotoxic effects, immunosuppression, and renoprotection effect. The molecular targets of these effects mainly contains GLUTs, SGLT1, GLP-1, FoxO1, TNF-α, IL-6, caspase-3, bcl-2, MDA, SOD, STAT5-PPAR gamma pathway, PI3K/Akt pathway, AMPK-JNK pathway, NF-κB pathway, and endoplasmic reticulum stress. Rg1, Rg3, Rb1, and compound K demonstrated the most promising therapeutic prospects as potential adjuvant medicines for the treatment of diabetes. This paper highlights the underlying pharmacological mechanisms of the

Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients

PubMed Central

Deserti, Marzia; Vasuri, Francesco; Farioli, Andrea; Degiovanni, Alessio; Palloni, Andrea; Frega, Giorgio; Barbera, Maria A.; de Lorenzo, Stefania; Garajova, Ingrid; Di Marco, Mariacristina; Pinna, Antonio D.; Cescon, Matteo; Cucchetti, Alessandro; Ercolani, Giorgio; D’Errico-Grigioni, Antonietta; Pantaleo, Maria A.; Biasco, Guido; Tavolari, Simona

2016-01-01

Background. The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involved in gemcitabine intracellular uptake. This study investigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. Methods. Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells. The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. Results. Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%) showed concomitant cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR 0.49, 95% CI 0.24–0.99, p = .046) than those who were negative or positive only in the cytoplasm of tumor cells. Notably, the association between DFS and membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two cycles: HR 0.96, 95% CI 0.34–2.68; three to four cycles: HR 0.99, 95% CI 0.34–2.90; five to six cycles: HR 0.27, 95% CI 0.10–0.77). Conclusion. hENT-1 localization on tumor cell membrane may predict response to adjuvant gemcitabine in CC patients receiving more than four cycles of chemotherapy. Further prospective randomized trials on larger populations are required to confirm these preliminary results, so that optimal gemcitabine-based chemotherapy may be tailored for CC patients in the adjuvant setting. Implications for Practice: Gemcitabine is becoming an increasingly used adjuvant modality in cholangiocarcinoma (CC), but limited data are

Membrane Localization of Human Equilibrative Nucleoside Transporter 1 in Tumor Cells May Predict Response to Adjuvant Gemcitabine in Resected Cholangiocarcinoma Patients.

PubMed

Brandi, Giovanni; Deserti, Marzia; Vasuri, Francesco; Farioli, Andrea; Degiovanni, Alessio; Palloni, Andrea; Frega, Giorgio; Barbera, Maria A; de Lorenzo, Stefania; Garajova, Ingrid; Di Marco, Mariacristina; Pinna, Antonio D; Cescon, Matteo; Cucchetti, Alessandro; Ercolani, Giorgio; D'Errico-Grigioni, Antonietta; Pantaleo, Maria A; Biasco, Guido; Tavolari, Simona

2016-05-01

The use of gemcitabine as an adjuvant modality for cholangiocarcinoma (CC) is increasing, but limited data are available on predictive biomarkers of response. Human equilibrative nucleoside transporter 1 (hENT-1) is the major transporter involved in gemcitabine intracellular uptake. This study investigated the putative predictive role of hENT-1 localization in tumor cells of CC patients undergoing treatment with adjuvant gemcitabine. Seventy-one consecutive patients with resected CC receiving adjuvant gemcitabine at our center were retrospectively analyzed by immunohistochemistry for hENT-1 localization in tumor cells. The main outcome measure was disease-free survival (DFS). Hazard ratios (HRs) of relapse and associated 95% confidence intervals (CIs) were obtained from proportional hazards regression models stratified on quintiles of propensity score. Twenty-three (32.4%) cases were negative for hENT-1, 22 (31.0%) were positive in the cytoplasm only, and 26 (36.6%) showed concomitant cytoplasm/membrane staining. Patients with membrane hENT-1 had a longer DFS (HR 0.49, 95% CI 0.24-0.99, p = .046) than those who were negative or positive only in the cytoplasm of tumor cells. Notably, the association between DFS and membrane hENT-1 was dependent on the number of gemcitabine cycles (one to two cycles: HR 0.96, 95% CI 0.34-2.68; three to four cycles: HR 0.99, 95% CI 0.34-2.90; five to six cycles: HR 0.27, 95% CI 0.10-0.77). hENT-1 localization on tumor cell membrane may predict response to adjuvant gemcitabine in CC patients receiving more than four cycles of chemotherapy. Further prospective randomized trials on larger populations are required to confirm these preliminary results, so that optimal gemcitabine-based chemotherapy may be tailored for CC patients in the adjuvant setting. Gemcitabine is becoming an increasingly used adjuvant modality in cholangiocarcinoma (CC), but limited data are available on predictive biomarkers of response. In this study, patients

Vaccines, adjuvants and autoimmunity.

PubMed

Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

2015-10-01

Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Restorative and synergistic efficacy of Kalpaamruthaa, a modified Siddha preparation, on an altered antioxidant status in adjuvant induced arthritic rat model.

PubMed

Mythilypriya, Rajendran; Shanthi, Palanivelu; Sachdanandam, Panchanatham

2007-07-20

Rheumatoid arthritis (RA) is a prevalent and debilitating disease that affects the joints. Infiltration of blood-derived cells in the affected joints upon activation generate reactive oxygen/nitrogen species, resulting in an oxidative stress. One approach to counteract this oxidative stress is the use of antioxidants as therapeutic agents. Kalpaamruthaa (KA), a modified indigenous Siddha preparation constituting Semecarpus anacardium nut milk extract (SA), Emblica officinalis (EO) and honey was evaluated for its synergistic antioxidant potential in adjuvant induced arthritic rats than sole SA treatment. Levels/activities of reactive oxygen species (ROS)/reactive nitrogen species (RNS), myeloperoxidase, lipid peroxide and enzymic and non-enzymic antioxidants were determined in control, arthritis induced, SA and KA treated (150 mg/kg b.wt.) animals. The levels/activities of ROS/RNS, myeloperoxidase and lipid peroxide were increased significantly (p<0.05) and the activities of enzymic and non-enzymic antioxidants were in turn decreased in arthritic rats, whereas these changes were reverted to near normal levels upon SA and KA treatment. KA showed an enhanced antioxidant potential than sole treatment of SA in adjuvant induced arthritic rats. KA via enhancing the antioxidant status in adjuvant induced arthritic rats than sole SA treatment proves to be an important therapeutic modality in the management of RA and thereby instituting the role of oxidative stress in the clinical manifestation of the disease RA. The profound antioxidant efficacy of KA than SA alone might be due to the synergistic action of the polyphenols such as flavonoids, tannins and other compounds such as vitamin C and hydroxycinnamates present in KA.

The efficacy of adjuvant trastuzumab in HER-2 positive breast cancer with axillary lymph node metastases according to the treatment duration.

PubMed

Sendur, Mehmet A N; Aksoy, Sercan; Ozdemir, Nuriye Y; Yazici, Ozan; Zengin, Nurullah; Altundag, Kadri

2014-12-01

Trastuzumab is the first anti-HER-2 humanized monoclonal antibody. The benefit of adjuvant trastuzumab has been shown in randomized phase III trials. Despite trastuzumab being recommended for 52 weeks in the adjuvant treatment of HER-2 positive breast cancer according to the current breast cancer guidelines, there is still no consensus on the optimal duration of adjuvant trastuzumab. The aim of our study is to investigate the efficacy and safety of adjuvant trastuzumab for 9 weeks and 52 weeks in axillary lymph node positive HER-2 positive breast cancer patients. A total of 271 HER-2 and axillary node positive breast cancer patients who received trastuzumab in adjuvant treatment between the years 2005 and 2013 were retrospectively analyzed. Patients with axillary node positive HER-2 positive breast cancer who were non-metastatic were enrolled to the study. Patients were allocated to the 9 week trastuzumab group (n = 155) or the 52 week trastuzumab group (n = 116). Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). Two-sided p values of <0.05 were considered statistically significant. The most important limitation of our manuscript is the retrospective design. The median follow-up time for this analysis was 34 (4-95) months. Patients' clinical and pathological characteristics were well balanced between the two treatment arms. In the 9 week trastuzumab treatment group, the DFS rate was 96.7%, 84.8% and 74.9% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 94.3%, 80.0% and 80.0% (P = 0.76). In the 9 week trastuzumab treatment group, the OS rate was 99.3%, 92.2% and 88.3% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 99.0%, 94.7% and 78.6% (P = 0.99). In both groups, symptomatic heart failure was not reported but asymptomatic left ventricular ejection fraction (LVEF) decline was observed 3 (1

The adoption of new adjuvant radiation therapy modalities among Medicare beneficiaries with breast cancer: clinical correlates and cost implications.

PubMed

Roberts, Kenneth B; Soulos, Pamela R; Herrin, Jeph; Yu, James B; Long, Jessica B; Dostaler, Edward; Gross, Cary P

2013-04-01

New radiation therapy modalities have broadened treatment options for older women with breast cancer, but it is unclear how clinical factors, geographic region, and physician preference affect the choice of radiation therapy modality. We used the Surveillance, Epidemiology, and End Results-Medicare database to identify women diagnosed with stage I-III breast cancer from 1998 to 2007 who underwent breast-conserving surgery. We assessed the temporal trends in, and costs of, the adoption of intensity modulated radiation therapy (IMRT) and brachytherapy. Using hierarchical logistic regression, we evaluated the relationship between the use of these new modalities and patient and regional characteristics. Of 35,060 patients, 69.9% received conventional external beam radiation therapy (EBRT). Although overall radiation therapy use remained constant, the use of IMRT increased from 0.0% to 12.6% from 1998 to 2007, and brachytherapy increased from 0.7% to 9.0%. The statistical variation in brachytherapy use attributable to the radiation oncologist and geographic region was 41.4% and 9.5%, respectively (for IMRT: 23.8% and 22.1%, respectively). Women undergoing treatment at a free-standing radiation facility were significantly more likely to receive IMRT than were women treated at a hospital-based facility (odds ratio for IMRT vs EBRT: 3.89 [95% confidence interval, 2.78-5.45]). No such association was seen for brachytherapy. The median radiation therapy cost per treated patient increased from $5389 in 2001 to $8539 in 2007. IMRT and brachytherapy use increased substantially from 1998 to 2007; overall, radiation therapy costs increased by more than 50%. Radiation oncologists played an important role in treatment choice for both types of radiation therapy, whereas geographic region played a bigger role in the use of IMRT than brachytherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

The Adoption of New Adjuvant Radiation Therapy Modalities Among Medicare Beneficiaries With Breast Cancer: Clinical Correlates and Cost Implications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, Kenneth B.; Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut; Soulos, Pamela R.

2013-04-01

Purpose: New radiation therapy modalities have broadened treatment options for older women with breast cancer, but it is unclear how clinical factors, geographic region, and physician preference affect the choice of radiation therapy modality. Methods and Materials: We used the Surveillance, Epidemiology, and End Results-Medicare database to identify women diagnosed with stage I-III breast cancer from 1998 to 2007 who underwent breast-conserving surgery. We assessed the temporal trends in, and costs of, the adoption of intensity modulated radiation therapy (IMRT) and brachytherapy. Using hierarchical logistic regression, we evaluated the relationship between the use of these new modalities and patient andmore » regional characteristics. Results: Of 35,060 patients, 69.9% received conventional external beam radiation therapy (EBRT). Although overall radiation therapy use remained constant, the use of IMRT increased from 0.0% to 12.6% from 1998 to 2007, and brachytherapy increased from 0.7% to 9.0%. The statistical variation in brachytherapy use attributable to the radiation oncologist and geographic region was 41.4% and 9.5%, respectively (for IMRT: 23.8% and 22.1%, respectively). Women undergoing treatment at a free-standing radiation facility were significantly more likely to receive IMRT than were women treated at a hospital-based facility (odds ratio for IMRT vs EBRT: 3.89 [95% confidence interval, 2.78-5.45]). No such association was seen for brachytherapy. The median radiation therapy cost per treated patient increased from $5389 in 2001 to $8539 in 2007. Conclusions: IMRT and brachytherapy use increased substantially from 1998 to 2007; overall, radiation therapy costs increased by more than 50%. Radiation oncologists played an important role in treatment choice for both types of radiation therapy, whereas geographic region played a bigger role in the use of IMRT than brachytherapy.« less

Near-Infrared Laser Adjuvant for Influenza Vaccine

PubMed Central

Kashiwagi, Satoshi; Yuan, Jianping; Forbes, Benjamin; Hibert, Mathew L.; Lee, Eugene L. Q.; Whicher, Laura; Goudie, Calum; Yang, Yuan; Chen, Tao; Edelblute, Beth; Collette, Brian; Edington, Laurel; Trussler, James; Nezivar, Jean; Leblanc, Pierre; Bronson, Roderick; Tsukada, Kosuke; Suematsu, Makoto; Dover, Jeffrey; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C.

2013-01-01

Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants. PMID:24349390

Light and laser treatment modalities for disseminated superficial actinic porokeratosis: a systematic review.

PubMed

Aird, Gregory A; Sitenga, Jenna L; Nguyen, Austin Huy; Vaudreuil, Adam; Huerter, Christopher J

2017-05-01

Treatment of disseminated superficial actinic porokeratosis (DSAP) is poorly standardized. The present review seeks to comprehensively discuss the potential for laser and light modalities in the treatment of DSAP. A systematic review of light and laser treatment modalities was conducted to include 26 cases of patients with DSAP. Systematic review resulted in 14 articles to be included. Photodynamic therapy (PDT) overall was the least successful treatment modality, with clinical improvement seen in a minority of patients (MAL-PDT: N = 9 patients, 33.3% showed improvement; ALA-PDT: N = 3 patients, 0% improvement; hypericin-PDT: N = 2 patients, 0% improvement) after numerous post-procedural side effects of hyperpigmentation, inflammation, erythema, and discomfort. Overall, in the available reports, PDT demonstrates poor outcomes with greater incidence of side effects. The response rates of DSAP lesions treated with lasers were as follows: (Q-switched ruby lasers: N = 2, 100%; CO 2 laser: N = 1, 100%; PDT and CO 2 combination therapy: N = 2, 0-50%; erbium and neodymium YAG lasers: N = 2, 100%; fractional 1927-nm thulium fiber lasers: N = 2, 100%; Grenz rays: N = 1, 100%; and fractional photothermolysis: N = 2, 100%). The side effects of laser therapy were minimal and included mild erythema, slight hyperpigmentation, and moderate edema. Laser therapy is a promising treatment option for DSAP with an excellent side effect profile. However, higher power studies are required to determine optimal guidelines for laser treatment of DSAP.

Bisphosphonates as adjuvant therapy for breast cancer.

PubMed

Burkinshaw, Roger; Coleman, Robert

2006-01-01

Great strides have been made over the last 20 years in the treatment of breast cancer and despite an increasing incidence, the number of deaths has fallen sharply since the late 1980s. The advent of new therapies, including taxanes and aromatase inhibitors, and exciting results announced recently using trastuzumab in the adjuvant treatment of HER2-positive patients should decrease this even further. However, although most patients present with disease that appears to be localized to the breast, a significant proportion of women will eventually develop metastatic breast cancer. Therefore, the detection and treatment of micrometastatic disease represents perhaps the most important remaining challenge in breast cancer management, and is the focus of extensive ongoing research. Bone is the most frequent site of distant relapse, accounting for approximately 40% of all first recurrences. In addition to the well recognized release of bone cell-activating factors from the tumor, it is now appreciated that the release of bone-derived growth factors and cytokines from resorbing bone can attract cancer cells to the bone surface and facilitate their growth and proliferation. Bisphosphonates are potent inhibitors of bone osteolysis and the inhibition of bone resorption could therefore have an effect on the development and progression of metastatic bone disease. They could represent an adjuvant therapeutic strategy of potential importance. Clinical trial results with the early bisphosphonate, clodronate, have proved inconclusive. A large, randomized, controlled trial has recently completed accrual and should provide the definitive answer to the question of the role of clodronate in this setting. More potent second- and third-generation bisphosphonates have also shown enhanced antitumor effects in preclinical evaluation and further studies are required to determine whether this antitumor potential of bisphosphonates translates to the clinical setting. Adjuvant bisphosphonates are

Same gain, less pain: potential patient preferences for adjuvant treatment in premenopausal women with early breast cancer.

PubMed

Fallowfield, Lesley; McGurk, Rhona; Dixon, Michael

2004-11-01

The aim of this study was to determine the treatment preferences (adjuvant goserelin or cyclophosphamide, methotrexate and fluorouracil (CMF) chemotherapy) of healthy premenopausal women should they hypothetically develop oestrogen-receptor (ER) positive early breast cancer. Two hundred pre or peri-menopausal women read two scenarios describing goserelin or chemotherapy. Information included: How and where treatments were administered, side-effects, their likely persistence and impact on fertility. Women stated their unprompted initial and final preferences with reasons for the choices made. Respondents showed an overwhelming preference for goserelin. 156 (78%) women favoured goserelin, 22 (11%) chemotherapy and 22 (11%) remained undecided (P<0.0001). Primary reasons for preferring goserelin for were 105 (71%) avoidance of chemotherapy side-effects, especially hair loss, perceived convenience and less disruption to normal life 54 (36%). The minority who preferred chemotherapy, valued the treatment finishing more quickly. These results together with clinical trial data showing equivalence of goserelin with CMF regimens suggest that premenopausal women with ER-positive tumours should at least be offered the choice of either adjuvant hormone therapy or chemotherapy.

An overview of clinical and experimental treatment modalities for port wine stains

PubMed Central

Chen, Jennifer K.; Ghasri, Pedram; Aguilar, Guillermo; van Drooge, Anne Margreet; Wolkerstorfer, Albert; Kelly, Kristen M.; Heger, Michal

2014-01-01

Port wine stains (PWS) are the most common vascular malformation of the skin, occurring in 0.3% to 0.5% of the population. Noninvasive laser irradiation with flashlamp-pumped pulsed dye lasers (selective photothermolysis) currently comprises the gold standard treatment of PWS; however, the majority of PWS fail to clear completely after selective photothermolysis. In this review, the clinically used PWS treatment modalities (pulsed dye lasers, alexandrite lasers, neodymium:yttrium-aluminum-garnet lasers, and intense pulsed light) and techniques (combination approaches, multiple passes, and epidermal cooling) are discussed. Retrospective analysis of clinical studies published between 1990 and 2011 was performed to determine therapeutic efficacies for each clinically used modality/technique. In addition, factors that have resulted in the high degree of therapeutic recalcitrance are identified, and emerging experimental treatment strategies are addressed, including the use of photodynamic therapy, immunomodulators, angiogenesis inhibitors, hypobaric pressure, and site-specific pharmaco-laser therapy. PMID:22305042

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

NASA Astrophysics Data System (ADS)

Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

Physical modalities in the treatment of neurological dysfunction.

PubMed

Galea, Mary P

2012-06-01

This chapter presents modalities of physical therapy used in optimizing sensorimotor recovery from nervous system injury. A brief historical perspective, rationale, indications for application, and evidence of effectiveness of various physical treatment modalities is provided. Many of the facilitatory and inhibitory techniques used in the past are no longer used, as they were based on an understanding of recovery after nervous system injury that is now outdated. There has been a paradigm shift in the management of people with neurological dysfunction. In particular there has been a reduction in focus on the positive features or the upper motor neuron syndrome, such as spasticity, and an increasing emphasis on active, task-related practice of functional tasks. Physical therapy for people with neurological disorders has undergone a paradigm shift as a result of new knowledge about motor control, skill acquisition, and recovery of function after injury. Future research should address new applications of electrical stimulation and whole body vibration as well as the optimal dosage and timing of interventions. Copyright © 2012 Elsevier B.V. All rights reserved.

Trismus following different treatment modalities for head and neck cancer: a systematic review of subjective measures.

PubMed

Loh, Sook Y; Mcleod, Robert W J; Elhassan, Hassan A

2017-07-01

The aim of this review was to compare systematically the subjective measure of trismus between different interventions to treat head and neck cancer, particularly those of the oropharynx. Using The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Guidelines, Six databases were searched for the text using various terms which include "oropharyngeal/head and neck cancer", "trismus/mouth opening" and the various treatment modalities. Included in the review were clinical studies (> or =10 patients). Three observers independently assessed the papers identified. Among the six studies reviewed, five showed a significantly worst outcome with regard to the quality-of-life questionnaire scores for a radiotherapy or surgery and radiotherapy (RT) ± chemotherapy or chemoradiotherapy when compared to surgery alone. Only one study showed no significant difference between surgery alone and other treatment modalities. Subjective quality-of-life measures are a concurrent part of modern surgical practice. Although subjective measures were utilised to measure post operative trismus successfully, there was no consensus as to which treatment modality had overall better outcomes, with conflicting studies in keeping with the current debate in this field. Larger and higher quality studies are needed to compare all three treatment modalities.

MO-B-BRC-00: Prostate HDR Treatment Planning - Considering Different Imaging Modalities

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2016-06-15

Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

Strategies for treatment of dystonia.

PubMed

Dressler, Dirk; Altenmueller, Eckart; Bhidayasiri, Roongroj; Bohlega, Saeed; Chana, Pedro; Chung, Tae Mo; Frucht, Steven; Garcia-Ruiz, Pedro J; Kaelin, Alain; Kaji, Ryuji; Kanovsky, Petr; Laskawi, Rainer; Micheli, Federico; Orlova, Olga; Relja, Maja; Rosales, Raymond; Slawek, Jaroslaw; Timerbaeva, Sofia; Warner, Thomas T; Saberi, Fereshte Adib

2016-03-01

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

An overview of clinical and experimental treatment modalities for port wine stains.

PubMed

Chen, Jennifer K; Ghasri, Pedram; Aguilar, Guillermo; van Drooge, Anne Margreet; Wolkerstorfer, Albert; Kelly, Kristen M; Heger, Michal

2012-08-01

Port wine stains (PWS) are the most common vascular malformation of the skin, occurring in 0.3% to 0.5% of the population. Noninvasive laser irradiation with flashlamp-pumped pulsed dye lasers (selective photothermolysis) currently comprises the gold standard treatment of PWS; however, the majority of PWS fail to clear completely after selective photothermolysis. In this review, the clinically used PWS treatment modalities (pulsed dye lasers, alexandrite lasers, neodymium:yttrium-aluminum-garnet lasers, and intense pulsed light) and techniques (combination approaches, multiple passes, and epidermal cooling) are discussed. Retrospective analysis of clinical studies published between 1990 and 2011 was performed to determine therapeutic efficacies for each clinically used modality/technique. In addition, factors that have resulted in the high degree of therapeutic recalcitrance are identified, and emerging experimental treatment strategies are addressed, including the use of photodynamic therapy, immunomodulators, angiogenesis inhibitors, hypobaric pressure, and site-specific pharmaco-laser therapy. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Adjuvant treatment with a symbiotic in patients with inflammatory non-allergic rhinitis.

PubMed

Gelardi, M; De Luca, C; Taliente, S; Fiorella, M L; Quaranta, N; Russo, C; Ciofalo, A; Macchi, A; Mancini, M; Rosso, P; Seccia, V; Guagnini, F; Ciprandi, G

2017-01-01

Inflammatory non-allergic rhinitis (INAR) is characterized by the presence of an inflammatory infiltrate and a non-IgE-mediated pathogenesis. This retrospective, controlled, multicentre study investigated whether a symbiotic, containing Lactobacillus acidophilus NCFM, Bifidobacterium lactis, and fructo-oligosaccharides (Pollagen®, Allergy Therapeutics, Italy), prescribed as adjunctive therapy to a standard pharmacological treatment, was able to reduce symptom severity, endoscopic features, and nasal cytology in 93 patients (49 males and 44 females, mean age 36.3±7.1 years) with INAR. The patients were treated with nasal corticosteroid, oral antihistamine, and isotonic saline. At randomization, 52 patients were treated also with symbiotic as adjunctive therapy, whereas the remaining 41 patients served as controls. Treatment lasted for 4 weeks. Patients were visited at baseline, after treatment, and after 4-week follow-up. Adjunctive symbiotic treatment significantly reduced the percentages of patients with symptoms and endoscopic signs, and diminished inflammatory cells. In conclusion, the present study demonstrates that a symbiotic was able, as adjuvant treatment, to significantly improve symptoms, endoscopic feature, and cytology in patients with INAR, and its effect may be long lasting.

Adjuvant therapy for advanced renal cell carcinoma.

PubMed

Meissner, Matthew A; McCormick, Barrett Z; Karam, Jose A; Wood, Christopher G

2018-07-01

Locally advanced, non-metastatic renal cell carcinoma (RCC) is conventionally managed with surgery. However, patients are at a high risk of RCC recurrence and have poor survival outcomes. An effective adjuvant systemic treatment is needed to improve on these outcomes. Targeted molecular and immune-based therapies have been investigated, or are under investigation, but their role in this setting remains unclear. Areas covered: A comprehensive search of PubMed and ClinicalTrials.gov was performed for relevant literature. The following topics pertinent to adjuvant therapy in RCC were evaluated: strategies for patient selection, cytokine-based immunotherapy, vaccine therapy, VEGF and non-VEGF targeted molecular agents, and immune checkpoint inhibitors. Expert commentary: Strong evidence for the incorporation of adjuvant therapy in high-risk RCC is lacking. Multiple targeted molecular therapies have been examined with only one approved for use. Genetic and molecular-based prognostic models are needed to determine who may benefit from adjuvant therapy. Developing adjuvant therapy strategies in the future depends on the results of important ongoing trials with immunotherapy and targeted agents.

The effectiveness of psychosocial modalities in the treatment of alcohol problems in adults: a review of the evidence.

PubMed

Martin, Garth W; Rehm, Jürgen

2012-06-01

Our objectives were to review the effectiveness of psychosocial modalities in the treatment of alcohol use disorders and problems, and to examine the impact of therapists on treatment outcome, the evidence on best practices for comorbid conditions, and the evidence on treatment matching. We based our review on published systematic reviews of this topic after 2000. There is strong evidence that some, but not all, psychosocial treatments are effective in treating alcohol problems. Those with the strongest empirical support are motivational enhancement therapy, various cognitive-behavioural interventions, and brief interventions. Meta-analyses for several of these modalities suggest typical effect sizes in the low-to-moderate range. When these modalities have been compared with one another in well-designed clinical trials, they have been shown to be of comparable effectiveness. There is little basis on which to recommend one of these modalities over another but good reason to select from among them.

Non-invasive different modalities of treatment for temporomandibular disorders: review of literature

PubMed Central

2018-01-01

Temporomandibular disorders (TMDs) are diseases that affect the temporomandibular joint and supporting structures. The goal of treatment for TMDs is elimination or reduction of pain and return to normal temporomandibular joint function. Initial treatment for TMDs is non-invasive and conservative, not surgical. Oral and maxillofacial surgeons should fully understand and actively care about non-invasive treatments for TMDs. The purpose of this study is to review the validity and outcomes of non-invasive and surgical treatment modalities for TMDs. PMID:29732308

Emerging Trends in Surgical and Adjuvant Radiation Therapies among Women Diagnosed with Ductal Carcinoma in Situ

PubMed Central

Shiyanbola, Oyewale O.; Sprague, Brian L.; Hampton, John M.; Dittus, Kim; James, Ted A.; Herschorn, Sally; Gangnon, Ronald E.; Weaver, Donald L.; Trentham-Dietz, Amy

2016-01-01

BACKGROUND The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. We sought to investigate recent patterns in DCIS treatment by demographic factors. METHODS Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group and geographic region. The likelihood of receiving specific treatment modalities was analyzed using multivariable logistic regression. RESULTS DCIS cases were most frequently treated with breast conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation following BCS plateaued at around 70% after 2007, with increasing utilization of mastectomy beyond 2005. Additionally, there was an increasing trend in post-mastectomy reconstruction over time, and women of African ancestry (odds ratio, 0.69; 95% confidence interval,0.66–0.72) and Hispanic women were less likely to undergo reconstruction (odds ratio, 0.83; 95% confidence interval, 0.78–0.89) compared to women of European ancestry. A similar trend was observed in contralateral risk reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk reducing mastectomy among all ancestral/ethnic groups. CONCLUSION Recent trends demonstrate a plateau in radiation therapy administration following BCS, with increasing utilization of mastectomy, reconstruction and contralateral risk reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. PMID:27244699

Adjuvant treatment with monosialoganglioside may improve neurological outcomes in neonatal hypoxic–ischemic encephalopathy: A meta-analysis of randomized controlled trials

PubMed Central

Sheng, Lei

2017-01-01

Background Ganglioside has a neuroprotective role in neonatal hypoxic–ischemic encephalopathy (HIE). This study aimed to evaluate the neurological outcomes of monosialoganglioside as adjuvant treatment for neonatal HIE by conducting a meta-analysis. Methods A comprehensive literature search was made in the Pubmed, EMBASE, Cochrane Library, Wanfang, CNKI, VIP databases through October 2016. Randomized controlled trials comparing monosialoganglioside with the usual treatment for newborns having HIE deemed eligible. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence interval (CI) were calculated for continuous and dichotomous data, respectively. Results Ten trials consisting of 787 neonates were included. Adjuvant treatment with monosialoganglioside significantly reduced major neurodevelopmental disabilities (RR = 0.35; 95% CI = 0.21–0.57), cerebral palsy (RR = 0.32; 95% CI = 0.12–0.87), mental retardation (RR = 0.31; 95% CI = 0.11–0.88) as well as improved the mental (WMD = 14.95; 95% CI = 7.44–22.46) and psychomotive (WMD = 13.40; 95% CI = 6.69–20.11) development index during the follow-up. Also, monosialoganglioside significantly improved Neonatal Behavioral Neurological Assessment scores (WMD = 2.91; 95% CI = 2.05–3.78) compared with the usual treatment. However, adverse effects associated with monosialoganglioside were poorly reported in the included trials. Conclusion Adjuvant treatment with monosialoganglioside had beneficial effects in improving neurological outcomes in neonatal HIE. However, these findings should be interpreted with caution because of methodological flaws in the included trials. Furthermore, safety of monosialoganglioside use should also be further evaluated. PMID:28832625

Utility of up-front transoral robotic surgery in tailoring adjuvant therapy.

PubMed

Gildener-Leapman, Neil; Kim, Jeehong; Abberbock, Shira; Choby, Garret W; Mandal, Rajarsi; Duvvuri, Umamaheswar; Ferris, Robert L; Kim, Seungwon

2016-08-01

The purpose of this study was to describe how the up-front transoral robotic surgery (TORS) approach could be used to individually tailor adjuvant therapy based on surgical pathology. Between January 2009 and December 2013, 76 patients received TORS for oropharyngeal squamous cell carcinoma (OPSCC). Clinical predictors of adjuvant therapy were analyzed and comparisons were made between recommended treatment guidelines for up-front surgery versus definitive nonsurgical approaches. Advanced N classification, human papillomavirus (HPV)-positive tumor, extracapsular spread (ECS; 26 of 76), perineural invasion (PNI; 14 of 76), and positive margins (7 of 76) were significant predictors of adjuvant chemoradiotherapy (CRT) (p < .05). Up-front TORS deintensified adjuvant therapy; 76% of stage I/II and 46% of stage III/IV patients avoided CRT. Conversely, pathologic staging resulted in 33% of patients who would have received radiotherapy (RT) alone based on clinical staging, to be intensified to receive adjuvant CRT. The TORS approach deintensifies adjuvant therapy and provides valuable pathologic information to intensify treatment in select patients. TORS may be less effective in deintensification of adjuvant therapy in patients with clinically advanced N classification disease. © 2016 Wiley Periodicals, Inc. Head Neck 38:1201-1207, 2016. © 2016 Wiley Periodicals, Inc.

Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer

PubMed Central

Advani, Pooja; Cornell, Lauren; Chumsri, Saranya; Moreno-Aspitia, Alvaro

2015-01-01

Human epidermal growth factor receptor 2 (HER2) is a tyrosine kinase transmembrane receptor that is overexpressed on the surface of 15%–20% of breast tumors and has been associated with poor prognosis. Consistently improved pathologic response and survival rates have been demonstrated with use of trastuzumab in combination with standard chemotherapy in both early and advanced breast cancer. However, resistance to trastuzumab may pose a major problem in the effective treatment of HER2-positive breast cancer. Dual HER2 blockade, using agents that work in a complimentary fashion to trastuzumab, has more recently been explored to evade resistance in both the preoperative (neoadjuvant) and adjuvant settings. Increased effectiveness of dual anti-HER2 agents over single blockade has been recently reported in clinical studies. Pertuzumab in combination with trastuzumab and taxane is currently approved in the metastatic and neoadjuvant treatment of HER2-positive breast cancer. Various biomarkers have also been investigated to identify subsets of patients with HER2-positive tumors who would likely respond best to these targeted therapy combinations. In this article, available trial data regarding efficacy and toxicity of treatment with combination HER2 agents in the neoadjuvant and adjuvant setting have been reviewed, and relevant correlative biomarker data from these trials have been discussed. PMID:26451122

Adjuvant bisphosphonate treatment for breast cancer: Where are we heading and can the pre-clinical literature help us get there?

PubMed

Russell, Kent; Clemons, Mark; Costa, Luis; Addison, Christina L

2012-06-01

Bisphosphonates have demonstrated anti-tumour activity in preclinical studies of bone metastatic disease, thus it was natural to transition these agents into the adjuvant cancer therapy setting. Surprisingly, the results of adjuvant breast cancer trials have shown either modest to no benefit or even harm. We sought to explore whether the preclinical results supporting bisphosphonate use provided clues to help explain the current clinical data. Interestingly, the majority of preclinical data suggested that bisphosphonate treatment was more efficacious when administered after the establishment of osseous metastases. This is similar to the findings of one clinical study whereby patients with biopsy evidence of osseous micrometastases derive greater survival benefit from bisphosphonate treatment. Another clinical study found bisphosphonates were associated with increased incidence of visceral metastases, similar to what has been previously published in preclinical models using "preventative" dosing strategies. While the current clinical data suggest bisphosphonates may be more efficacious in post-menopausal or oestrogen depleted patients, or those with hormone receptor positive tumours, to date no appropriately designed preclinical studies have evaluated these effects. Furthermore, putative mechanisms that regulate response to bisphosphonates in other tumour types remain to be evaluated in breast cancer. Despite the initial optimism regarding adjuvant bisphosphonate therapy, the conflicting clinical results from large trials suggest that we should return to the bench to further investigate factors that may influence response to bisphosphonate treatment or identify appropriate characteristics that would indicate the sub-groups of patients most likely to benefit from bisphosphonate treatment.

A geriatrician's guide to the use of the physical modalities in the treatment of pain and dysfunction.

PubMed

Perret, Danielle Marie; Rim, Josephine; Cristian, Adrian

2006-05-01

The use of the physical modalities in the treatment of musculoskeletal conditions has a long and rich history. This article explores the various physical modalities and their indications, precautions, and contraindications, especially in their applied use in pain management. It also highlights the role of the physical modalities as agents for the management of pain in the geriatric population.

Non-pharmacological treatment options for refractory epilepsy: an overview of human treatment modalities and their potential utility in dogs.

PubMed

Martlé, Valentine; Van Ham, Luc; Raedt, Robrecht; Vonck, Kristl; Boon, Paul; Bhatti, Sofie

2014-03-01

Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Probiotics as an adjuvant treatment in Helicobacter pylori eradication therapy.

PubMed

Zhu, Xin Yan; Liu, Fei

2017-04-01

Over 80% of individuals infected with Helicobacter pylori (H. pylori) are asymptomatic. Increased resistance to antibiotics and decreased compliance to the therapeutic regimens have led to the failure of eradication therapy. Probiotics, with direct and indirect inhibitory effects on H. pylori in both animal models and clinical trials, have recently been used as a supplementary treatment in H. pylori eradication therapy. Probiotics have been considered useful because of the improvements in H. pylori eradication rates and therapy-related side effects although treatment outcomes using probiotics are controversial due to the heterogeneity of species, strains, doses and therapeutic duration of probiotics. Thus, despite the positive role of probiotics, several factors need to be further considered during their applications. Moreover, adverse events of probiotic use need to be noted. Further investigations into the safety of adjuvant probiotics to H. pylori eradication therapy are required. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Role of Adjuvant Chemoradiation Therapy in Adenocarcinomas of the Ampulla of Vater

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnan, Sunil; Rana, Vishal; Evans, Douglas B.

2008-03-01

Purpose: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. Methods and Materials: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies weremore » used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). Results: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). Conclusions: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.« less

Pathogenesis and treatment of pseudofolliculitis barbae.

PubMed

Brown, L A

1983-10-01

Pseudofolliculitis barbae is a condition in which a foreign body inflammatory reaction surrounds an ingrown hair. Shaving is the major cause, especially in persons with wavy or curly hair. Among black men who shave, the disease is of particular concern because of both social pressures and limited medical understanding concerning its treatment. The pathogenesis of the disease as well as treatment modalities are presented. General measures, as well as specific techniques involving use of electric clippers, chemical depilatories, manual razors, and complete epilation are discussed. Adjuvant measures are presented such as antibiotics and, in very special cases, retinoic acid.

Opinions about Treatment Modalities among Patients Involuntarily Committed to a Forensic Psychiatric Hospital in Finland

ERIC Educational Resources Information Center

Repo-Tiihonen, Eila; Vuorio, Osmo; Koivisto, Hanna; Paavola, Paula; Hakola, Panu

2004-01-01

Patient satisfaction studies concerning various treatment modalities are few among involuntary forensic psychiatric treatment. They indicate general satisfaction with medication, interactive treatment and occupational therapy but dissatisfaction with lack of privacy, insufficiently explained rules and inadequately explained reasons of seclusion.…

Chemoradiotherapy versus chemotherapy as adjuvant treatment for localized gastric cancer: a propensity score-matched analysis.

PubMed

Girardi, Daniel M; de Lima, Mariana A; Pereira, Gabriel C B; Negrão, Marcelo V; López, Rossana V M; Capareli, Fernanda C; Sabbaga, Jorge; Hoff, Paulo Marcelo G

2018-04-03

Treatment of localized gastric cancer (LGC) consists of surgical resection followed by adjuvant treatment. Both chemoradiation (CRT) and chemotherapy (CT) regimens have shown benefit in survival outcomes versus observation. However, there are few data comparing these approaches. This study included consecutive patients with LGC treated at Instituto do Cancer do Estado de Sao Paulo (ICESP) from 2012 to 2015. CRT was based on the INT-0116 regimen and CT consisted of a platinum and fluoropyrimidine doublet. Treatment choice was based on physician preference. Toxicity was evaluated for every cycle. Overall survival (OS) analysis was performed by Kaplan-Meier. A propensity score-matched analysis was performed to minimize selection bias. A total of 309 patients were evaluated, 227 in CRT group and 82 in CT group. The most prevalent grade 3/4 toxicities in CRT and CT groups were: nausea/vomiting (9.25 vs 4.9%), fatigue (9.3% vs 2.4%), mucositis (4.4% vs 1.2%), neutropenia (37.8% vs 20.9%), febrile neutropenia (3.9% vs 0%), anemia (4.3% vs 6.1%), thrombocytopenia (2.6% vs 4.9%), neuropathy (0 vs 2.4%) and hand-foot syndrome (0.4% vs 2.4%). Two grade 5 toxicities (febrile neutropenia and anemia) occurred in CRT group. There was no difference in the pattern of recurrence. After a median follow-up of 23.5 months (CRT) and 20.6 months (CT), there was no difference in OS between groups. CT and CRT present similar efficacy and tolerability as adjuvant treatment for LGC.

Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

PubMed Central

Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

2014-01-01

Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities.

PubMed

Crinière, Emmanuelle; Kaloshi, Gentian; Laigle-Donadey, Florence; Lejeune, Julie; Auger, Nathalie; Benouaich-Amiel, Alexandra; Everhard, Sibille; Mokhtari, Karima; Polivka, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khê; Thillet, Joëlle; Sanson, Marc

2007-06-01

MGMT promoter methylation, which has been correlated with the response to alkylating agents, was investigated in a retrospective series of 219 glioblastomas (GBMs) treated with various modalities. MGMT methylation had no impact on survival for the whole group, but showed a significant advantage (17.1 months vs. 13.1) for patients treated with RT+ adjuvant chemotherapy (relative risk of death (RR) = 0.53; P = 0.041), particularly when patients received CT during the course of RT (MS = 19.9 months vs. 12.5 months; RR = 0.227, P = 0.001). This suggests that the prognostic impact of MGMT methylation is dependent on therapeutic modalities and schedules. MGMT methylation was not correlated with the main molecular alterations, such as 10q loss and p53 expression.

Curcuminoids as EBV Lytic Activators for Adjuvant Treatment in EBV-Positive Carcinomas

PubMed Central

Ramayanti, Octavia; Brinkkemper, Mitch; Verkuijlen, Sandra A. W. M.; Ritmaleni, Leni; Go, Mei Lin

2018-01-01

Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA. Curcumin, a dietary spice used in Asian countries, is known for its antitumor property and therapeutic potential. Novel curcuminoids that were developed to increase efficacy and bioavailability may serve as oral CLVA adjuvants. We investigated the potential of curcumin and its analogs (curcuminoids) to trigger the EBV lytic cycle in EBVaGC and NPC cells. EBV-reactivating effects were measured by immunoblot and immunofluorescence using monoclonal antibodies specific for EBV lytic proteins. Two of the hit compounds (41, EF24) with high lytic inducing activity were further studied for their synergistic or antagonistic effects when combined with GCb+VPA and analyzed by cytotoxicity and mRNA profiling assays to measure the EBV reactivation. Curcuminoid as a single agent significantly induced EBV reactivation in recombinant GC and NPC lines. The drug effects were dose- and time-dependent. Micromolar concentration of curcuminoid EF24 enhanced the CLVA effect in all cell systems except SNU719, a naturally infected EBVaGC cell that carries a more tightly latent viral genome. These findings indicated that EF24 has potential as EBV lytic activator and may serve as an adjuvant in CLVA treatment. PMID:29565326

Curcuminoids as EBV Lytic Activators for Adjuvant Treatment in EBV-Positive Carcinomas.

PubMed

Ramayanti, Octavia; Brinkkemper, Mitch; Verkuijlen, Sandra A W M; Ritmaleni, Leni; Go, Mei Lin; Middeldorp, Jaap M

2018-03-22

Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA. Curcumin, a dietary spice used in Asian countries, is known for its antitumor property and therapeutic potential. Novel curcuminoids that were developed to increase efficacy and bioavailability may serve as oral CLVA adjuvants. We investigated the potential of curcumin and its analogs (curcuminoids) to trigger the EBV lytic cycle in EBVaGC and NPC cells. EBV-reactivating effects were measured by immunoblot and immunofluorescence using monoclonal antibodies specific for EBV lytic proteins. Two of the hit compounds ( 41 , EF24 ) with high lytic inducing activity were further studied for their synergistic or antagonistic effects when combined with GCb+VPA and analyzed by cytotoxicity and mRNA profiling assays to measure the EBV reactivation. Curcuminoid as a single agent significantly induced EBV reactivation in recombinant GC and NPC lines. The drug effects were dose- and time-dependent. Micromolar concentration of curcuminoid EF24 enhanced the CLVA effect in all cell systems except SNU719, a naturally infected EBVaGC cell that carries a more tightly latent viral genome. These findings indicated that EF24 has potential as EBV lytic activator and may serve as an adjuvant in CLVA treatment.

Advances in diagnostic and treatment modalities for intracranial tumors.

PubMed

Dickinson, P J

2014-01-01

Intracranial neoplasia is a common clinical condition in domestic companion animals, particularly in dogs. Application of advances in standard diagnostic and therapeutic modalities together with a broad interest in the development of novel translational therapeutic strategies in dogs has resulted in clinically relevant improvements in outcome for many canine patients. This review highlights the status of current diagnostic and therapeutic approaches to intracranial neoplasia and areas of novel treatment currently in development. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma.

PubMed

Finocchiaro, L M E; Glikin, G C

2008-02-01

We evaluated the safety, efficacy and anti-tumor effects of a surgery adjuvant treatment on canine patients with malignant melanoma. This approach combined suicide gene therapy with a subcutaneous vaccine composed by formolized tumor cells and irradiated xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. The post-surgical margin of the cavity was infiltrated with lipid-complexed thymidine kinase suicide gene coadministrated with ganciclovir. Toxicity was minimal or absent in all patients. With respect to surgery-treated controls (SC), this combined treatment (CT) significantly increased the fraction of patients local disease-free from 6 to 58% and distant metastases-free from 43 to 78% (Fisher's Exact test). In addition, CT significantly improved both SC overall 78 (23-540) and metastasis-free survival 112 (0-467) days to more than 1312 days (respective ranges: 43-1312 and 0-1312) (Kaplan-Meier analysis). In those patients subjected to partial surgery or presenting local recurrence, the efficacy of CT was verified by a 49% of objective responses that averaged 85% of tumor mass loss, while 22% displayed tumor progression as 94% of SC did. Therefore, surgery adjuvant CT controlled tumor growth, delaying or preventing post-surgical recurrence and distant metastasis, significantly extending survival and recovering the quality of life.

Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer.

PubMed

Garrison, Louis P; Lubeck, Deborah; Lalla, Deepa; Paton, Virginia; Dueck, Amylou; Perez, Edith A

2007-08-01

Adding trastuzumab to adjuvant chemotherapy provides significant clinical benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A cost-effectiveness analysis was performed to assess clinical and economic implications of adding trastuzumab to adjuvant chemotherapy, based upon joint analysis of NSABP B-31 and NCCTG N9831 trials. A Markov model with 4 health states was used to estimate the cost utility for a 50-year-old woman on the basis of trial results through 4 years and estimates of long-term recurrence and death based on a meta-analysis of trials. From 6 years onward, rates of recurrence and death were assumed to be the same in both trastuzumab and chemotherapy-only arms. Incremental costs were estimated for diagnostic and treatment-related costs. Analyses were from payer and societal perspectives, and these analyses were projected to lifetime and 20-year horizons. Over a lifetime, the projected cost of trastuzumab per quality-adjusted life year (QALY; discount rate 3%) gained was 26,417 dollars (range 9,104 dollars-69,340 dollars under multiway sensitivity analysis). Discounted incremental lifetime cost was 44,923 dollars, and projected life expectancy was 3 years longer for patients who received trastuzumab (19.4 years vs 16.4 years). During a 20-year horizon, the projected cost of adding trastuzumab to chemotherapy was 34,201 dollars per QALY gained. Key cost-effectiveness drivers were discount rate, trastuzumab price, and probability of metastasis. The cost-effectiveness result was robust to sensitivity analysis. Trastuzumab for adjuvant treatment of early stage breast cancer was projected to be cost effective over a lifetime horizon, achieving a cost-effectiveness ratio below that of many widely accepted oncology treatments. (c) 2007 American Cancer Society.

[Adjuvant cryosurgery in the treatment of unicameral bone cysts].

PubMed

Tena-Sanabria, Mario Edgar; Hernández-Hernández, Melissa Jesús; Tena-González, Mario Edgar; Mejía-Aranguré, Juan Manuel

2014-01-01

Multiple treatments have been used for the unicameral bone cyst lesion, such as steroid application, multiple perforations, bone curettages, partial resection and bone grafting. The purpose of this study was to describe the evolution of children with unicameral bone cyst who were treated with cryosurgery as coadjuvant therapy. Cross-sectional descriptive study over the period between January 2001 and December 2006. Twelve patients were studied and treated at the Pediatric Orthopedics Department of the Pediatrics Hospital at the Centro Médico Nacional Siglo XXI. Twelve patients were analyzed; all of them were treated with curettage, cryotherapy and bone grafting. In 7 patients, the lesions were located in the humerus (58.3 %), in 3 in the tibia (25 %), in 1 in the ilio-ischiopubic branch (8.3 %), and in 1 in the clavicle (8.3 %). Follow-up ranged from 12 to 36 months. Bone healing required 2 to 3 months after the surgery; the response was complete in 9 (75 %) patients and partial in 3 (25 %). Function was restored in all cases, without recurrences. Cryosurgery as an adjuvant treatment and autologous or homologous bone grafting prevented local recurrence of unicameral bone cyst lesions, favored bone healing and allowed for a full range of motion functionality without complications.

Induction of protective and therapeutic antitumor immunity by a DNA vaccine with C3d as a molecular adjuvant.

PubMed

Xu, Gui-lian; Zhang, Ke-qin; Guo, Bo; Zhao, Ting-ting; Yang, Fei; Jiang, Man; Wang, Qing-hong; Shang, Yu-hang; Wu, Yu-zhang

2010-10-18

Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer therapies is unclear. In this study, we have engineered a DNA vaccine that expresses extracellular region of murine VEGFR-2 (FLK1(265-2493)) and 3 copies of C3d (C3d3), a component of complement as a molecular adjuvant, designed to increase antitumor immunity. VEGFR-2 has a more restricted expression on endothelial cells and is upregulated once these cells proliferate during angiogenesis in the tumor vasculature. Immunization of mice with vector encoding FLK1(265-2493) alone generated only background levels of anti-VEGFR-2 antibodies and slight inhibitory effect on tumor growth. However, the addition of C3d3 to the vaccine construct significantly augmented the anti-VEGFR-2 humoral immune response and inhibited the tumor growth. The antitumor activity induced by vaccination with vector encoding FLK1(265-2493)-C3d3 fusion protein was also demonstrated via growth inhibition of established tumors following passive transfer of immune serum from vaccinated mice. Our results suggest that vaccination with vector encoding FLK1(265-2493) with C3d3 as a molecular adjuvant induces adaptive humoral activity, which is directed against the murine VEGFR-2 and can significantly inhibit tumor growth, and that administration of C3d as a molecular adjuvant to increase antibodies levels to VEGFR-2 may provide an alternative treatment modality for cancer therapies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

Primary mucosal sinonasal melanoma—Case report and review of the literature. The role of complex treatment-surgery and adjuvant radiotherapy

PubMed Central

Marinova, Lena; Yordanov, Kaloyan; Sapundgiev, Nikolay

2010-01-01

Aim The place of adjuvant radiotherapy in the treatment of sinonasal melanoma. Background Sinonasal mucosal melanoma is a rare disease with poor prognosis and requires a complex treatment. Elective neck dissection in patients with N0 and adjuvant radiotherapy has been a source of controversy. High late regional recurrence rates rise questions about elective irradiation of the neck nodes in patients with N0 stage disease. Methods We present our two years’ follow up in a case of locally advanced sinonasal melanoma and literature review of the treatment options for mucosal melanoma. Results In locally advanced sinonasal melanoma treated with surgical resection, postoperative radiotherapy and chemotherapy we had local tumor control. Two years later, a regional contralateral recurrence without distant metastasis occurred. Conclusions Literature data for frequent neck lymph nodes recurrences justify elective neck dissection. Postoperative elective neck radiotherapy for patients with locally advanced sinonasal melanoma and clinically N0 appears to decrease the rate of late regional recurrences. PMID:24376954

Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis.

PubMed

Tang, Monica; Price, Timothy Jay; Shapiro, Jeremy; Gibbs, Peter; Haller, Daniel G; Arnold, Dirk; Peeters, Marc; Segelov, Eva; Roy, Amitesh; Tebbutt, Niall; Pavlakis, Nick; Karapetis, Chris; Burge, Matthew

2018-04-01

Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.

Adjuvant chemotherapy for breast cancer patients: patients' expectations and physicians' attitudes.

PubMed

Barak, Frida; Ostrowsky, Lev A; Kreitler, Shulamith

2012-06-01

Findings show that there is a certain degree of refusal on the part of breast cancer patients to undergo adjuvant therapy. Accordingly, the major goals of the study were, first, to learn more about the beliefs of breast cancer patients in regard to adjuvant therapy; second, to find out about the sources of the patients' beliefs; and third, to learn about the attitudes of oncologists concerning the same aspects of adjuvant therapy to which the patients' beliefs referred. The participants were 92 breast cancer patients (mean age 61.2) and 57 doctors of both genders specialized in oncology or affiliated domains. Both groups were administered questionnaires referring to goals of adjuvant treatment, the chances of attaining these goals, side effects, and difficulty of the treatment. Doctors were specifically asked about the views they thought proper to communicate to patients in regard to the mentioned issues. Patients were also asked about whether they had doubts about the treatment and sources of information. The findings showed disparities between the views of patients and doctors in regard to goals, chances of attainment, side effects, and difficulty of treatment. Patients endorsed more goals than doctors and tended to assign to them lower chances of attainment. Doctors were divided in their views about whether to communicate the side effects and difficulties. The results reveal the importance of outlining goals for patients undergoing adjuvant treatment and the disagreements between doctors about what should be communicated to patients, and highlight the complexity of providing to patients information that is both scientifically correct and emotionally helpful.

How do surgeons decide to refer patients for adjuvant cancer treatment? Protocol for a qualitative study

PubMed Central

2012-01-01

Background Non-small cell lung cancer, breast cancer, and colorectal cancer are commonly diagnosed cancers in Canada. Patients diagnosed with early-stage non-small cell lung, breast, or colorectal cancer represent potentially curable populations. For these patients, surgery is the primary mode of treatment, with (neo)adjuvant therapies (e.g., chemotherapy, radiotherapy) recommended according to disease stage. Data from our research in Nova Scotia, as well as others’, demonstrate that a substantial proportion of non-small cell lung cancer and colorectal cancer patients, for whom practice guidelines recommend (neo)adjuvant therapy, are not referred for an oncologist consultation. Conversely, surveillance data and clinical experience suggest that breast cancer patients have much higher referral rates. Since surgery is the primary treatment, the surgeon plays a major role in referring patients to oncologists. Thus, an improved understanding of how surgeons make decisions related to oncology services is important to developing strategies to optimize referral rates. Few studies have examined decision making for (neo)adjuvant therapy from the perspective of the cancer surgeon. This study will use qualitative methods to examine decision-making processes related to referral to oncology services for individuals diagnosed with potentially curable non-small cell lung, breast, or colorectal cancer. Methods A qualitative study will be conducted, guided by the principles of grounded theory. The study design is informed by our ongoing research, as well as a model of access to health services. The method of data collection will be in-depth, semi structured interviews. We will attempt to recruit all lung, breast, and/or colorectal cancer surgeons in Nova Scotia (n ≈ 42), with the aim of interviewing a minimum of 34 surgeons. Interviews will be audiotaped and transcribed verbatim. Data will be collected and analyzed concurrently, with two investigators independently coding

Choice of treatment modalities was not influenced by pain, severity or co-morbidity in patients with knee osteoarthritis.

PubMed

Jamtvedt, Gro; Dahm, Kristin Thuve; Holm, Inger; Odegaard-Jensen, Jan; Flottorp, Signe

2010-03-01

Patients with knee osteoarthritis (OA) are commonly treated by physiotherapists in primary care. The physiotherapists use different treatment modalities. In a previous study, we identified variation in the use of transcutaneous electrical nerve stimulation (TENS), low level laser or acupuncture, massage and weight reduction advice for patients with knee OA. The purpose of this study was to examine factors that might explain variation in treatment modalities for patients with knee OA. Practising physiotherapists prospectively collected data for one patient with knee osteoarthritis each through 12 treatment sessions.We chose to examine factors that might explain variation in the choice of treatment modalities supported by high or moderate quality evidence, and modalities which were frequently used but which were not supported by evidence from systematic reviews. Experienced clinicians proposed factors that they thought might explain the variation in the choice of these specific treatments. We used these factors in explanatory analyses. Using TENS, low level laser or acupuncture was significantly associated with having searched databases to help answer clinical questions in the last six months (odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.08-3.42). Not having Internet access at work and using more than four treatment modalities were significant determinants for giving massage (OR = 0.36, 95% CI = 0.19-0.68 and OR = 8.92, 95% CI = 4.37-18.21, respectively). Being a female therapist significantly increased the odds for providing weight reduction advice (OR = 3.60, 95% CI = 1.12-11.57). No patient characteristics, such as age, pain or co-morbidity, were significantly associated with variation in practice. Factors related to patient characteristics, such as pain severity and co-morbidity, did not seem to explain variation in treatment modalities for patients with knee OA. Variation was associated with the following factors: physiotherapists having Internet

Non-ablative fractional resurfacing in combination with topical tretinoin cream as a field treatment modality for multiple actinic keratosis: a pilot study and a review of other field treatment modalities.

PubMed

Prens, Sebastiaan P; de Vries, Karin; Neumann, H A Martino; Prens, Errol P

2013-06-01

Actinic keratoses (AK) are premalignant lesions occurring mainly in sun-damaged skin. Current topical treatment options for AK and photo-damaged skin such as liquid nitrogen and electrosurgery are not suitable for field treatment. Otherwise, therapies suitable for field treatment bring along considerable patient discomfort. Non-ablative fractional resurfacing has emerged as a logical treatment option especially for field treatment of AK. To evaluate the clinical efficacy of fractional laser therapy for clearing AK and improving skin quality. To compare patient friendliness of the "fractional" therapy with those reported for other field treatment modalities. Ten patients with Fitzpatrick skin type I to III with multiple AK and extensive sun-damaged skin, received 5-10 sessions with a 4-week interval using a 1550 nm Erbium-Glass Fractionated laser (Sellas, Korea). Four weeks and 24 weeks after the last treatment the clinical results were evaluated by an independent physician. The mean degree of improvement, in terms of reduction in the number of AK and improvement of skin texture, was 54% on a 4 point PGA scale, and persisted for approximately 6 months. The biggest advantage of fractional laser treatment, besides the eradication of AK and a clear rejuvenation effect, is the absence of "downtime". Fractional non-ablative resurfacing induces significant reduction in the number of AK and improves the skin quality. Also all patients preferred fractional laser therapy above other AK treatment modalities.

Emerging trends in surgical and adjuvant radiation therapies among women diagnosed with ductal carcinoma in situ.

PubMed

Shiyanbola, Oyewale O; Sprague, Brian L; Hampton, John M; Dittus, Kim; James, Ted A; Herschorn, Sally; Gangnon, Ronald E; Weaver, Donald L; Trentham-Dietz, Amy

2016-09-15

The use of surgery and radiation therapy in treating ductal carcinoma in situ (DCIS) is directed by treatment guidelines and evidence from research. This study investigated recent patterns in DCIS treatment by demographic factors. Data for women diagnosed with DCIS between 1998 and 2011 (n = 416,232) in the National Cancer Data Base were assessed for trends in treatment patterns by age group, calendar year, ancestral/ethnic group, and geographic region. The likelihood of receiving specific treatment modalities was analyzed with multivariable logistic regression. DCIS cases were most frequently treated with breast-conserving surgery (BCS) and adjuvant radiation (45.6%). After an initial rise, the use of adjuvant radiation after BCS plateaued at approximately 70% after 2007, with increasing utilization of mastectomy beyond 2005. In addition, there was an increasing trend in postmastectomy reconstruction over time, and women of African ancestry (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72) and Hispanic women (OR, 0.83; 95% CI, 0.78-0.89) were less likely to undergo reconstruction in comparison with women of European ancestry. A similar trend was observed in contralateral risk-reducing mastectomy utilization, with women of European ancestry having a more rapid rise in the utilization of contralateral risk-reducing mastectomy in comparison with all other ancestral/ethnic groups. Recent trends demonstrate a plateau in radiation therapy administration after BCS along with increasing utilization of mastectomy, reconstruction, and contralateral risk-reducing mastectomy. There are substantial differences in treatment utilization according to ancestry/ethnicity and geographical region. Further studies examining patient-physician decision making surrounding DCIS treatment are warranted. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2810-2818. © 2016 American Cancer Society. © 2016 American Cancer Society.

Treatment modality preferences and adherence to group treatment for panic disorder with agoraphobia.

PubMed

Perreault, Michel; Julien, Dominic; White, Noé Djawn; Bélanger, Claude; Marchand, André; Katerelos, Theodora; Milton, Diana

2014-06-01

To examine the relationship between preference for group psychotherapy and adherence to group cognitive-behavioral therapy (CBT) for clients with panic disorder with agoraphobia (PDA), 109 participants experiencing PDA completed a questionnaire measuring preference for group treatment (PGTQ) before beginning CBT groups. A t test was used to compare preference scores for group treatment to investigate whether participants who completed treatment differed from those who abandoned treatment. Participants who completed group therapy expressed higher preference for group treatment than participants who dropped out of treatment (t[107] = 1.99; p < 0.05). The PGTQ-4 presented adequate psychometric properties. Reliability analyses of the items retained after factorization demonstrated an acceptable level of internal consistency (Cronbach's alpha of 0.76). Preference for individual or group therapy appears to impact treatment retention for patients with PDA. Matching patients' preferences to the type of treatment modality used appears to be pertinent, especially for the treatment of anxiety disorders. In terms of practical implications, the rationale and benefits of group therapy should be explained to participants reluctant to engage in group therapy. Individual intervention or a combination of group and individual treatment could be considered for clients who are likely to drop out of group therapy.

Treatment modalities and medication recommended by health care professionals for treating recurrent herpes labialis.

PubMed

Raborn, G Wayne; Chan, Karen S; Grace, Michael

2004-01-01

The authors conducted a survey to determine how health care professionals respond to patients' inquiries about cold sores, also known as recurrent herpes labialis, and their choices of treatment modalities and medications. The authors mailed a one-page, pretested survey to a random sample of dentists, pharmacists and family physicians in Alberta, Canada. After receiving ethics approval from the University of Alberta, Edmonton, the authors mailed 998 surveys. The response rate was 51 percent. Topical antiviral medication was the most common treatment recommended (63 percent). Over-the-counter medication was the first choice for pharmacists (83 percent) as compared with dentists (15 percent) and physicians (16 percent). Emotional stress (60 percent) was reported by patients to be the most common trigger, and pain or discomfort (81 percent) was their primary concern. Acyclovir ointment was the most common antiviral drug recommended or prescribed by health care professionals (60 percent), and cost was the major reason they gave for not recommending or prescribing antiviral drugs (73 percent). The authors found variation in treatment modalities and recommendations by each health profession, despite the fact that patients reported similar triggers and concerns. This may be due to individual patient need and the health care professional's lack of knowledge. Survey results may serve as a reference for health care professionals to use to determine how their choices of medications and treatment modalities compare with those of other practitioners. Professionals should know the benefits and limitations of all therapies, discuss them with the patients and select a treatment.

Adjuvant interferon-α for the treatment of high-risk melanoma: An individual patient data meta-analysis.

PubMed

Ives, Natalie J; Suciu, Stefan; Eggermont, Alexander M M; Kirkwood, John; Lorigan, Paul; Markovic, Svetomir N; Garbe, Claus; Wheatley, Keith

2017-09-01

Many randomised trials assessing interferon-α (IFN-α) as adjuvant therapy for high-risk malignant melanoma have been undertaken. To better assess the role of IFN-α, an individual patient data (IPD) meta-analysis of these trials was undertaken. IPD was sought from all randomised trials of adjuvant IFN-α versus no IFN-α for high-risk melanoma. Primary outcomes were event-free survival (EFS) and overall survival (OS). Standard methods for quantitative IPD meta-analysis were used. Subgroup analyses by dose, duration of treatment and various patient and disease-specific parameters were performed. Fifteen trials were included in the analysis (eleven with IPD). EFS was significantly improved with IFN-α (hazard ratio [HR] = 0.86, CI 0.81-0.91; P < 0.00001), as was OS (HR = 0.90, CI 0.85-0.97; P = 0.003). The absolute differences in EFS at 5 and 10 years were 3.5% and 2.7%, and for OS were 3.0% and 2.8% respectively in favour of IFN-α. There was no evidence that the benefit of IFN-α differed depending on dose or duration of treatment, or by age, gender, site of primary tumour, disease stage, Breslow thickness, or presence of clinical nodes. Only for ulceration was there evidence of an interaction (test for heterogeneity: P = 0.04 for EFS; P = 0.002 for OS); only patients with ulcerated tumours appeared to obtain benefit from IFN-α. This meta-analysis provides clear evidence that adjuvant IFN-α significantly reduces the risk of relapse and improves survival and shows no benefit for higher doses compared to lower doses. The increased benefit in patients with ulcerated tumours, and lack of benefit in patients without ulceration, needs further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hyperbaric Oxygen Therapy—A Novel Treatment Modality in Oral Submucous Fibrosis: A Review

PubMed Central

Kumar, M. Ashwini; Radhika, Besta; Reddy, Satya Prakash; Yaga, Uday Shankar

2015-01-01

Oral submucous fibrosis (OSMF) is a chronic, debilitating disease characterized by juxta epithelial fibrosis of the oral cavity and regarded as a potentially malignant disorder. Numerous treatment modalities ranging from various drugs to behavioral therapy have been tried with inconsistent results with varying degrees of success reflecting low predictability, requiring further evaluation and standardization. Novel treatment modality such as Hyperbaric oxygen therapy (HBOT) involves inhalation of 100% oxygen at increased atmospheric pressure usually ranging between 2.0 and 2.5 atmospheres for periods between 60 and 120 min. HBOT which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve hypoxic environment of OSMF and also possesses potent anti-inflammatory properties. This article enlightens on possible beneficial effects of HBOT in the management of OSMF at cellular and molecular level. PMID:26155590

Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

PubMed

Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

2018-02-01

The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

PubMed

Martinelli, F; Bogani, G; Ditto, A; Carcangiu, M; Papadia, A; Lecce, F; Chiappa, V; Lorusso, D; Raspagliesi, F

2015-08-01

Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adjuvant Treatment after Surgery in Stage IIIA Endometrial Adenocarcinoma

PubMed Central

Yoon, Mee Sun; Huh, Seung Jae; Kim, Hak Jae; Kim, Young Seok; Kim, Yong Bae; Kim, Joo-Young; Lee, Jong-Hoon; Kim, Hun Jung; Cha, Jihye; Kim, Jin Hee; Kim, Juree; Yoon, Won Sup; Choi, Jin Hwa; Chun, Mison; Choi, Youngmin; Lee, Kang Kyoo; Kim, Myungsoo; Jeong, Jae-Uk; Chang, Sei Kyung; Park, Won

2016-01-01

Purpose We evaluated the role of adjuvant therapy in stage IIIA endometrioid adenocarcinoma patients who underwent surgery followed by radiotherapy (RT) alone or chemoradiotherapy (CTRT) according to risk group. Materials and Methods A multicenter retrospective study was conducted including patients with surgical stage IIIA endometrial cancertreated by radical surgery and adjuvant RT or CTRT. Disease-free survival (DFS) and overall survival (OS) were analyzed. Results Ninety-three patients with stage IIIA disease were identified. Nineteen patients (20.4%) experienced recurrence, mostly distant metastasis (17.2%). Combined CTRT did not affect DFS (74.1% vs. 82.4%, p=0.130) or OS (96.3% vs. 91.9%, p=0.262) in stage IIIA disease compared with RT alone. Patients with age ≥ 60 years, grade G2/3, and lymphovascular space involvement had a significantly worse DFS and those variables were defined as risk factors. The high-risk group showed a significant reduction in 5-year DFS (≥ 2 risk factors) (49.0% vs. 88.0%, p < 0.001) compared with the low-risk group (< 2). Multivariate analysis confirmed that more than one risk factor was the only predictor of worse DFS (hazard ratio, 5.45; 95% confidence interval, 2.12 to 13.98; p < 0.001). Of patients with no risk factors, a subset treated with RT alone showed an excellent 5-year DFS and OS (93.8% and 100%, respectively). Conclusion We identified a low-risk subset of stage IIIA endometrioid adenocarcinoma patients who might be reasonable candidates for adjuvant RT alone. Further randomized studies are needed to determine which subset might benefit from combined CTRT. PMID:26511800

A Novel Therapeutic Modality for Advanced Stage Prostate Cancer Treatment

DTIC Science & Technology

2017-10-01

Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of...PrCa are non-selective and provide only limited response rate Thus, novel treatment modalities are needed to treat advanced stage PrCa. In this...of ORM on MTA1 protein. Considering effective therapeutic index of ORM, we are also making more potent analogues of ORM. These findings suggest that

Efficacy of temozolomide as adjuvant chemotherapy after postsurgical radiotherapy alone for glioblastomas.

PubMed

Rhee, Deok-Joo; Kong, Doo-Sik; Kim, Won Seog; Park, Kwon-Byong; Lee, Jung-Il; Suh, Yeon-Lim; Song, Sang Young; Kim, Sung Tae; Lim, Do-Hoon; Park, Kwan; Kim, Jong Hyun; Nam, Do-Hyun

2009-11-01

The aim of this study was to assess the efficacy of adjuvant TMZ chemotherapy for newly diagnosed GBM patients who were treated with surgery followed by radiotherapy alone. Between January 2003 and April 2005, 59 consecutive GBM patients underwent radiation therapy after surgical resection and subsequently received TMZ chemotherapy. For the comparative analysis, we selected 60 clinically matched GBM patients who underwent radiotherapy followed by nitrosourea-based chemotherapy (NUBC), at the same institution between June 1995 and April 2005. The study cohort was divided into two groups, those with adjuvant TMZ treatment and with NUBC. 59 patients with adjuvant TMZ treatment were assigned to the treatment group and 60 patients with NUBC to the control group. The median overall survival for the treatment group was 18.2 months (95% CI, 11.7-24.7 months), compared with the survival of 14.5 months (95% CI, 11.2-17.7 months) for the control group (p=0.019). The progression-free survival for the treatment group was 5.6 months (95% CI, 4.4-6.7 months), while the control group showed progression-free survival of 3.3 months (95% CT, 3.2-6.0 months) (p=0.030). Uni- and multivariate analysis revealed that extent of surgical resection, age > or =55 years and postoperative KPS were significantly associated with survival. Adjuvant TMZ chemotherapy provided a clinically relevant benefit of survival, as compared with NUBC. Thus, we suggest that adjuvant TMZ chemotherapy may be effective even for patients who did not receive concomitant chemoradiotherapy for GBM.

Treatment modalities for burning mouth syndrome: a systematic review.

PubMed

de Souza, Isadora Follak; Mármora, Belkiss Câmara; Rados, Pantelis Varvaki; Visioli, Fernanda

2018-06-01

In the burning mouth syndrome (BMS), patients experience a burning sensation in the oral cavity with no associated injury or clinical manifestation. The etiology of this condition is still poorly understood, and therefore, treatment is challenging. The aim of this study is to perform a systematic review of treatment possibilities described in the literature for BMS. PubMed, Embase, and SciELO databases were searched for randomized clinical trials published between 1996 and 2016. Following application of inclusion and exclusion criteria, 29 papers were analyzed and divided into five subcategories according to the type of treatment described: antidepressants, alpha-lipoic acid, phytotherapeutic agents, analgesic and anti-inflammatory agents, and non-pharmacological therapies. In each category, the results found were compared with regard to the methodology employed, sample size, assessment method, presence or absence of adverse effects, and treatment outcomes. The analysis revealed that the use of antidepressants and alpha-lipoic acid has been showing promising results; however, more studies are necessary before we can have a first-line treatment strategy for patients with BMS. To review systematically the literature about Burning Mouth Syndrome treatment may aid the clinicians to choose the treatment modality to improve patients symptoms based on the best evidence.

Different treatment modalities for refractory vaginismus in western Saudi Arabia.

PubMed

Fageeh, Wafa M K

2011-06-01

Although vaginismus is a common sexual dysfunction in Saudi Arabia, there are limited data concerning the treatment modalities associated with patients with symptoms of vaginismus. This study is aimed to evaluate the presentation and different modalities of management in patients with severe refractory vaginismus in western Saudi Arabia. Successful penetrative sexual intercourse suggesting that common elements of the therapies used were successful. A retrospective study of patients presenting with severe refractory vaginismus treated in Jeddah, Saudi Arabia. The subjects were 15 women with third to fourth degree vaginismus who presented to King Abdulazziz University Hospital between January 1, 2008 and January 1, 2009. The mean age of the participants was 23 years. The mean duration of marriage before seeking medical advice was 12 months. Six patients had undergone conventional therapy successfully. The other six cases, four of which had a previous history of treatment failure, and two who were unresponsive to 4 months of conventional therapy were offered botulinum toxin type A. Five patients who received the Botox therapy had satisfactory intercourse on the same day of the treatment. One patient required a repeat injection after 2 months for recurrent vaginismus. Three of the 15 patients refused the treatment as they were already divorced and had only come in to exclude organic causes for their condition. Vaginismus is an overlooked topic in conservative societies such as Saudi Arabia. For most patients, not knowing who to confide in or where to turn to plays a major role in the under diagnosis of vaginismus. Conventional therapy proved effective in mild and moderate cases, while botulinum toxin has a more rapid effect and was thus more effective in severe cases. © 2011 International Society for Sexual Medicine.

Ocular sarcoidosis: new diagnostic modalities and treatment.

PubMed

Yang, Sung J; Salek, Sherveen; Rosenbaum, James T

2017-09-01

Ocular involvement in sarcoidosis is present in up to 80% of patients and is frequently manifested before diagnosis of the underlying systemic disease. Considering the therapeutic consequences, early diagnosis of the underlying disease is advantageous in patients presenting with ocular inflammation. There are several ocular findings suggestive of underlying sarcoidosis, such as granulomatous keratic precipitates, iris nodules, cells in the vitreous humor known as snowballs and snowbanks, and retinal periphlebitis. High suspicion is crucial for the diagnosis of sarcoidosis. This review on ocular sarcoidosis will mainly focus on new diagnostic and treatment modalities. Recent studies found possible new diagnostic indicators for the diagnosis of ocular sarcoidosis which include not only serum profiles but also vitreous sample analysis. Ophthalmologic imaging techniques have improved to investigate the ocular structure in detail. Results from recent uveitis clinical trials have included sarcoidosis as an underlying cause and have reported positive results. The diagnosis of ocular sarcoidosis can be challenging in some cases. High suspicion is important to diagnose ocular sarcoidosis with various laboratory and ophthalmic tools. There are many possible options for the treatment of ocular sarcoidosis including various biologic agents.

Motivation and Readiness for Drug Treatment: Differences by Modality and Special Populations

PubMed Central

Melnick, Gerald; Hawke, Josephine; De Leon, George

2014-01-01

The purpose of this research is to expand our knowledge of motivational factors among admissions to various substance abuse treatment modalities and among those entering special programs. Differences in motivation are reported in a convenience sample of over 6000 admissions to 38 programs. Results from multilevel analyses show (1) an ordered increase in motivation by settings from referral to out patient, to methadone maintenance, to highest levels in residential programs; (2) significantly lower motivation among admissions to programs for special populations. Results are discussed in relation to the demand characteristics of treatment and non-recovery reasons for entering treatment. PMID:24735224

Motivation and readiness for drug treatment: differences by modality and special populations.

PubMed

Melnick, Gerald; Hawke, Josephine; De Leon, George

2014-01-01

The purpose of this research is to expand our knowledge of motivational factors among admissions to various substance abuse treatment modalities and among those entering special programs. Differences in motivation are reported in a convenience sample of more than 6,000 admissions to 38 programs. Results from multilevel analyses show (a) an ordered increase in motivation by settings from referral to outpatient, to methadone maintenance, and to the highest levels in residential programs and (b) significantly lower motivation among admissions to programs for special populations. Results are discussed in relation to the demand characteristics of treatment and non-recovery reasons for entering treatment.

Treatment of adjuvant arthritis with granulocyte-colony stimulating factor and peptide derived from heat shock protein 65.

PubMed

Brendolan, Andrea; Higuchi, Masanori; Sibley, Richard; Strober, Samuel

2003-01-01

Adjuvant arthritis in Lewis rats is induced by the subcutaneous injection of Mycobacterium tuberculosis in mineral oil, and the predominant T cell immune reactivity is against the heat shock protein 65 derived peptide 176-190. We treated Lewis rats with human recombinant G-CSF followed by (i.v) administration of peptide 176-190 after induction of adjuvant arthritis (AA), and observed decreased disease severity, joint destruction, new bone formation and joint ankylosis. Treatment with G-CSF alone was also effective, but to a lesser extent. In addition, we found that splenocytes from rats treated with G-CSF had reduced antigen presenting capacity compared with splenocytes from vehicle treated rats. Primed lymph node cells from G-CSF plus peptide treated rats showed a marked reduction in proliferation and secretion of IFN-gamma after stimulation with the heat shock protein peptide in vitro as compared to controls.

Management of localized and locally advanced renal tumors. A contemporary review of current treatment options.

PubMed

Brookman-May, S; Langenhuijsen, J F; Volpe, A; Minervini, A; Joniau, S; Salagierski, M; Roscigno, M; Akdogan, B; Vandromme, A; Rodriguez-Faba, O; Marszalek, M

2013-06-01

About 70% of patients with renal cell carcinoma present with localized or locally advanced disease at primary diagnosis. Whereas these patients are potentially curable by surgical treatment alone, a further 20% to 30% of patients are diagnosed with primary metastatic disease. Although over the past years medical treatment for metastatic patients has nearly completely changed from immunotherapy to effective treatment with targeted agents, metastatic disease still represents a disease status which is not curable. Also in patients with metastatic disease, surgical treatment of the primary tumor plays an important role, since local tumor related complications can be avoided or minimized by surgery. Furthermore, also improvement of overall survival has been proven for surgery in metastatic patients when combined with cytokine treatment. Hence, surgical combined with systemic treatment as a multi-modal, adjuvant, and neo-adjuvant treatment is also required in patients with advanced or metastatic disease. A growing number of elderly and comorbid patients are currently diagnosed with small renal masses, which has led to increased attention paid to alternative ablative treatment modalities as well as active surveillance strategies, which are applied in order to avoid unnecessary overtreatment in these patients. Since surgical treatment also might enhance the risk of chronic kidney disease with consecutive cardiac disorders as well as reduced overall survival, ablative techniques and active surveillance are increasingly applied. In this review article we focus on current surgical and none-surgical treatment options for the management of patients with localized, locally advanced, and metastatic renal cell carcinoma.

Childhood Enuresis: Current Diagnostic Formulations, Salient Findings, and Effective Treatment Modalities.

PubMed

Thurber, Steven

2017-06-01

Enuresis constitutes a frequently encountered problem area for children that may adversely affect social and emotional adjustment. This type of incontinence has been of concern to the human family for centuries. A brief history of enuresis is presented followed by current conceptualizations, diagnostic criteria, prevalence rates and psychiatric comorbidities. Historic notions of causation together with ineffective, sometimes barbaric treatments are then discussed, ending with a presentation of evidence-based treatment modalities, with the urine alarm being an essential element of effective treatment. An intervention termed dry bed training combines the urine alarm with a series of procedures designed in part to reduce relapse potential and should be a primary consideration for implementation by treatment professionals. Finally, a brief case study is presented illustrating special etiological and treatment considerations with juvenile psychiatric patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Tamoxifen with ovarian function suppression versus tamoxifen alone as an adjuvant treatment for premenopausal breast cancer: a meta-analysis of published randomized controlled trials

PubMed Central

Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei

2015-01-01

Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867

Current and emerging therapeutic modalities for hyperhidrosis, part 1: conservative and noninvasive treatments.

PubMed

Ram, Ramin; Lowe, Nicholas J; Yamauchi, Paul S

2007-03-01

Approximately 1% to 3% of the US population has hyperhidrosis (HH). HH can be an incapacitating medical condition because it not only hinders patient quality of life but also causes the secondary effect of excess cutaneous sweat. There is a broad spectrum of treatment modalities including topical and systemic therapies, iontophoresis, localized neuroinhibitory injections, and surgical interventions. This article reviews HH and the conservative treatments for the condition.

Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

PubMed Central

Sugarbaker, Paul H.; Bijelic, Lana

2012-01-01

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC) was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement. PMID:22888340

Geographic Variation in the Use of Adjuvant Therapy among Elderly Patients with Resected Non-Small Cell Lung Cancer

PubMed Central

Tien, Yu-Yu; Wright, Kara; Halfdanarson, Thorvardur R.; Abu-Hejleh, Taher; Brooks, John M.

2016-01-01

Objectives The purpose of this study was to assess to what extent geographic variation in adjuvant treatment for non-small cell lung cancer (NSCLC) patients would remain, after controlling for patient and area-level characteristics. Materials and Methods A retrospective cohort of 18,410 Medicare beneficiaries with resected, stage I-IIIA NSCLC was identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Adjuvant therapies were classified as adjuvant chemotherapy (ACT), postoperative radiation therapy (PORT), or no adjuvant therapy. Predicted treatment probabilities were estimated for each patient given their clinical, demographic, and area-level characteristics with multivariate logistic regression. Area Treatment Ratios were used to estimate the propensity of patients in a local area to receive an adjuvant treatment, controlling for characteristics of patients in the area. Areas were categorized as low-, mid- and high-use and mapped for two representative SEER registries. Results Overall, 10%, 12%, and 78% of patients received ACT, PORT and no adjuvant therapy, respectively. Age, sex, stage, type and year of surgery, and comorbidity were associated with adjuvant treatment use. Even after adjusting for patient characteristics, substantial geographic treatment variation remained. High- and low-use areas were tightly juxtaposed within and across SEER registries, often within the same county. In some local areas, patients were up to eight times more likely to receive adjuvant therapy than expected, given their characteristics. On the other hand, almost a quarter of patients lived in local areas in which patients were more than three times less likely to receive ACT than would be predicted. Conclusion Controlling for patient and area-level covariates did not remove geographic variation in adjuvant therapies for resected NSCLC patients. A greater proportion of patients were treated less than expected, rather than more than expected

T Helper 1–Inducing Adjuvant Protects against Experimental Paracoccidioidomycosis

PubMed Central

de Oliveira, Leandro Licursi; Coltri, Kely Cristine; Cardoso, Cristina Ribeiro Barros; Roque-Barreira, Maria-Cristina; Panunto-Castelo, Ademilson

2008-01-01

Immunostimulatory therapy is a promising approach to improving the treatment of systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug therapy is usually prolonged and associated with toxic side effects and relapses. The current study was undertaken to determine if the injection of a T helper (Th) 1–stimulating adjuvant in P. brasiliensis–infected mice could have a beneficial effect on the course of experimental PCM. For this purpose, mice were infected and treated with complete Freund's adjuvant (CFA), a well-established Th1 experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented a mild infection in the lungs characterized by absence of epithelioid cell granulomas and yeast cells, whereas the control mice presented multiple sites of focal epithelioid granulomas with lymphomonocytic halos circumscribing a high number of viable and nonviable yeast cells. In addition, CFA administration induced a 2.4 log reduction (>99%) in the fungal burden when compared to the control group, and led to an improvement of immune response, reversing the immunosuppression observed in the control group. The immunotherapy with Th1-inducing adjuvant, approved to be used in humans, might be a valuable tool in the treatment of PCM and potentially useful to improve the clinical cure rate in humans. PMID:18335066

Pilot study of acupuncture for the treatment of joint symptoms related to adjuvant aromatase inhibitor therapy in postmenopausal breast cancer patients.

PubMed

Crew, Katherine D; Capodice, Jillian L; Greenlee, Heather; Apollo, Arlyn; Jacobson, Judith S; Raptis, George; Blozie, Kimberly; Sierra, Alex; Hershman, Dawn L

2007-12-01

Aromatase inhibitors (AIs) have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. However, patients receiving AIs may experience joint symptoms, which may lead to early discontinuation of this effective therapy. We hypothesize that acupuncture is a safe and effective treatment for AI-induced arthralgias. Postmenopausal women with early-stage breast cancer who had self-reported musculoskeletal pain related to adjuvant AI therapy were randomized in a crossover study to receive acupuncture twice weekly for 6 weeks followed by observation or vice-versa. The intervention included full body and auricular acupuncture, and a joint-specific point prescription. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life measure, and serum levels of inflammatory markers, IL-1 beta and TNF-alpha. Twenty-one women were enrolled and two discontinued early. From baseline to the end of treatment, patients reported improvement in the mean BPI-SF worst pain scores (5.3 to 3.3, p = 0.01), pain severity (3.7 to 2.5, p = 0.02), and pain-related functional interference (3.1 to 1.7, p = 0.02), as well as the WOMAC function subscale and FACT-G physical well-being (p = 0.02 and 0.04, respectively). No adverse events were reported. In this pilot study, acupuncture reduced AI-related joint symptoms and improved functional ability and was well-tolerated. Musculoskeletal side effects are common among breast cancer survivors on adjuvant AI therapy, therefore, effective treatments are needed for symptom relief and to improve adherence to these life-saving medications.

Kinesio taping compared to physical therapy modalities for the treatment of shoulder impingement syndrome.

PubMed

Kaya, Erkan; Zinnuroglu, Murat; Tugcu, Ilknur

2011-02-01

The purpose of this study was to determine and compare the efficacy of kinesio tape and physical therapy modalities in patients with shoulder impingement syndrome. Patients (n = 55) were treated with kinesio tape (n = 30) three times by intervals of 3 days or a daily program of local modalities (n = 25) for 2 weeks. Response to treatment was evaluated with the Disability of Arm, Shoulder, and Hand scale. Patients were questioned for the night pain, daily pain, and pain with motion. Outcome measures except for the Disability of Arm, Shoulder, and Hand scale were assessed at baseline, first, and second weeks of the treatment. Disability of Arm, Shoulder, and Hand scale was evaluated only before and after the treatment. Disability of Arm, Shoulder, and Hand scale and visual analog scale scores decreased significantly in both treatment groups as compared with the baseline levels. The rest, night, and movement median pain scores of the kinesio taping (20, 40, and 50, respectively) group were statistically significantly lower (p values were 0.001, 0.01, and 0.001, respectively) at the first week examination as compared with the physical therapy group (50, 70, and 70, respectively). However, there was no significant difference in the same parameters between two groups at the second week (0.109, 0.07, and 0.218 for rest, night, and movement median pain scores, respectively). Disability of Arm, Shoulder, and Hand scale scores of the kinesio taping group were significantly lower at the second week as compared with the physical therapy group. No side effects were observed. Kinesio tape has been found to be more effective than the local modalities at the first week and was similarly effective at the second week of the treatment. Kinesio taping may be an alternative treatment option in the treatment of shoulder impingement syndrome especially when an immediate effect is needed.

Psychological trauma symptoms and Type 2 diabetes prevalence, glucose control, and treatment modality among American Indians in the Strong Heart Family Study

PubMed Central

Jacob, Michelle M.; Gonzales, Kelly L.; Calhoun, Darren; Beals, Janette; Muller, Clemma Jacobsen; Goldberg, Jack; Nelson, Lonnie; Welty, Thomas K.; Howard, Barbara V.

2013-01-01

Aims The aims of this paper are to examine the relationship between psychological trauma symptoms and Type 2 diabetes prevalence, glucose control, and treatment modality among 3,776 American Indians in Phase V of the Strong Heart Family Study. Methods This cross-sectional analysis measured psychological trauma symptoms using the National Anxiety Disorder Screening Day instrument, diabetes by American Diabetes Association criteria, and treatment modality by four categories: no medication, oral medication only, insulin only, or both oral medication and insulin. We used binary logistic regression to evaluate the association between psychological trauma symptoms and diabetes prevalence. We used ordinary least squares regression to evaluate the association between psychological trauma symptoms and glucose control. We used binary logistic regression to model the association of psychological trauma symptoms with treatment modality. Results Neither diabetes prevalence (22-31%; p = 0.19) nor control (8.0-8.6; p = 0.25) varied significantly by psychological trauma symptoms categories. However, diabetes treatment modality was associated with psychological trauma symptoms categories, as people with greater burden used either no medication, or both oral and insulin medications (odds ratio = 3.1, p < 0.001). Conclusions The positive relationship between treatment modality and psychological trauma symptoms suggests future research investigate patient and provider treatment decision making. PMID:24051029

Effect of Treatment Modality on Long-Term Outcomes in Attention-Deficit/Hyperactivity Disorder: A Systematic Review

PubMed Central

Arnold, L. Eugene; Hodgkins, Paul; Caci, Hervé; Kahle, Jennifer; Young, Susan

2015-01-01

Background Evaluation of treatments for attention-deficit/hyperactivity disorder (ADHD) previously focused on symptom control, but attention has shifted to functional outcomes. The effect of different ADHD treatment periods and modalities (pharmacological, non-pharmacological, and combination) on long-term outcomes needs to be more comprehensively understood. Methods A systematic search of 12 literature databases using Cochrane’s guidelines yielded 403 English-language peer-reviewed, primary studies reporting long-term outcomes (≥2 years). We evaluated relative effects of treatment modalities and durations and effect sizes of outcomes reported as statistically significantly improved with treatment. Results The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes. A majority of outcomes improved regardless of age of treatment initiation (60%–75%) or treatment duration (62%–72%). Studies with short treatment duration had shorter follow-up times (mean 3.2 years total study length) than those with longer treatment durations (mean 7.1 years total study length). Studies with follow-up times <3 years reported benefit with treatment for 93% of outcomes, whereas those with follow-up times ≥3 years reported treatment benefit for 57% of outcomes. Post-hoc analysis indicated that this result was related to the measurement of outcomes at longer periods (3.2 versus 0.4 years) after treatment cessation in studies with longer total study length. Conclusions While the majority of long-term outcomes of ADHD improve with all treatment modalities, the combination of pharmacological and non-pharmacological treatment was most consistently associated with improved long-term outcomes and large effect sizes. Older treatment initiation age

Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions.

PubMed

Andia, Isabel; Abate, Michele

2018-04-01

Current research on common musculoskeletal problems, including osteoarticular conditions, tendinopathies, and muscle injuries, focuses on regenerative translational medicine. Platelet-rich plasma therapies have emerged as a potential approach to enhance tissue repair and regeneration. Platelet-rich plasma application aims to provide supraphysiological concentrations of platelets and optionally leukocytes at injured/pathological tissues mimicking the initial stages of healing. However, the efficacy of platelet-rich plasma is controversial in chronic diseases because patients' outcomes show partial improvements. Platelet-rich plasma can be customized to specific conditions by selecting the most appropriate formulation and timing for application or by combining platelet-rich plasma with synergistic or complementary treatments. To achieve this goal, researchers should identify and enhance the main mechanisms of healing. In this review, the interactions between platelet-rich plasma and healing mechanisms were addressed and research opportunities for customized treatment modalities were outlined. The development of combinational platelet-rich plasma treatments that can be used safely and effectively to manipulate healing mechanisms would be valuable and would provide insights into the processes involved in physiological healing and pathological failure.

[Dengzhan Xixin injection as an adjuvant treatment for angina pectoris: a systematic review and Meta-analysis of randomized controlled trials].

PubMed

Wang, Feng-jiao; Xie, Yan-ming; Liao, Xing; Jia, Min

2015-08-01

The paper is to systematically evaluate the efficacy and safety of Deng Zhan Xi Xin injection ( DZXXI) as an adjuvant treatment for patients with angina pectoris. The Cochrane Library, Medline, EMbase, CBM, CNKI, VIP, and Wan fang Data base were searched. Randomized controlled trials (RCTs) of DZXXI combined with western medicine routine treatment versus western medicine routine treatment alone for angina pectoris patients were all included. All trials were assessed according to the Cochrane Reviewer' s Handbook 5.1 for Systematic Reviews of Intervention and Meta analyses were performed by RevMan 5. 2 Software. A total of 30RCTs (3 086 patients including 1 572 patients of treatment group and 1 514 patients of control group) were included. Meta-analysis of treatment group compared with control group showed superior effect over reducing cardiovascular events ( OR = 0.33; 95% CI: [0.16, 0.67], P = 0.002, improving effective rate of DZXXI as adjuvant treatment for angina pectoris patients (OR = 3.97; 95% CI: [3.15, 5.02]; P < 0.000 010 and electrocardiogram curative effect (OR = 2.21; 95% CI; [1.83, 2.68]; P < 0.000 010. Funnel figure seemed that there was publication bias. The current limited evidence showed that when compared with the control group, treatment group was superior in improving patients with angina pectoris. But based on the limitations of the study, rigorous design with long follow up clinical trials are necessary for further evidence.

Association Between Adjuvant Chemotherapy and Overall Survival in Patients With Rectal Cancer and Pathological Complete Response After Neoadjuvant Chemotherapy and Resection.

PubMed

Dossa, Fahima; Acuna, Sergio A; Rickles, Aaron S; Berho, Mariana; Wexner, Steven D; Quereshy, Fayez A; Baxter, Nancy N; Chadi, Sami A

2018-04-19

Although American guidelines recommend use of adjuvant chemotherapy in patients with locally advanced rectal cancer, individuals who achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy are less likely to receive adjuvant treatment than incomplete responders. The association and resection of adjuvant chemotherapy with survival in patients with pCR is unclear. To determine whether patients with locally advanced rectal cancer who achieve pCR after neoadjuvant chemoradiation therapy and resection benefit from the administration of adjuvant chemotherapy. This retrospective propensity score-matched cohort study identified patients with locally advanced rectal cancer from the National Cancer Database from 2006 through 2012. We selected patients with nonmetastatic invasive rectal cancer who achieved pCR after neoadjuvant chemoradiation therapy and resection. We matched patients who received adjuvant chemotherapy to patients who did not receive adjuvant treatment in a 1:1 ratio. We separately matched subgroups of patients with node-positive disease before treatment and node-negative disease before treatment to investigate for effect modification by pretreatment nodal status. We compared overall survival between groups using Kaplan-Meier survival methods and Cox proportional hazards models. We identified 2455 patients (mean age, 59.5 years; 59.8% men) with rectal cancer with pCR after neoadjuvant chemoradiation therapy and resection. We matched 667 patients with pCR who received adjuvant chemotherapy and at least 8 weeks of follow-up after surgery to patients with pCR who did not receive adjuvant treatment. Over a median follow-up of 3.1 years (interquartile range, 1.94-4.40 years), patients treated with adjuvant chemotherapy demonstrated better overall survival than those who did not receive adjuvant treatment (hazard ratio, 0.44; 95% CI, 0.28-0.70). When stratified by pretreatment nodal status, only those patients with pretreatment node

Dexamethasone as adjuvant therapy in the treatment of invasive meningococcal diseases.

PubMed

Tolaj, Ilir; Dreshaj, Shemsedin; Qehaja, Emine; Tolaj, Jasmina; Doda-Ejupi, Teuta; Mehmeti, Murat

2010-01-01

With this study we want to evaluate the role of dexamethasone adjuvant treatment in different clinical forms of invasive meningococcal diseases. WORK METHODS: This was a randomized, open label trial that was conducted in 147 individuals with meningococcal sepsis. All of the cases have been divided in two groups: (1) Cases with meningococcal disease and CNS infection, and (2) Cases with meningococcal disease and no affection of the CNS. Cases from both groups were treated with dexamethasone, 0.15 mg/kg, every 6 h, for 4 (four) days, as adjuvant therapy. Cases which were not treated with dexamethasone were used as control group. From overall number of cases, in 130 of them, the meningococcal disease was accompanied with meningitis; in other 17 cases only signs of sepsis were present. In both clinical forms, the dexamethasone was used in 92 cases. The higher mortality rate is registered among the cases without meningitis, 17.65%, compared with 6.92% which is registered among cases with meningitis. The overall mortality rate among all cases was 8.2%. The significant difference was recorded only on CSF sugar level between two groups (treated or not with dexamethasone) on the day 1-4 of the hospitalization. Our epidemiological data are in correlation with data from other epidemiological studies. Most of the cases 69.4%, were more than 12 hours sick at home before the hospitalization, 7.5 % of cases were hospitalized within 12 hours from the onset of the diseases, while 23.1% of cases data are missing. This is in correlation with similar data from other studies. Dexamethasone has a limited effect on outcome of the invasive meningococcal disease. Dexamethasone had some effect only during the days of administration in cases with clinical form of sepsis with meningitis, by normalizing the values of CSF sugar earlier.

[Pay attention to the application of the international intraocular retinoblastoma classification and sequential multiple modality treatment].

PubMed

Fan, X Q

2017-08-11

Retinoblastoma (RB) is the most common intraocular malignancy in childhood. It may seriously affect vision, and even threaten the life. The early diagnosis rate of RB in China remains low, and the majority of patients are at late phase with high rates of enucleation and mortality. The International Intraocular Retinoblastoma Classification and TNM staging system are guidances for therapeutic choices and bases for prognosis evaluation. Based on the sequential multi-method treatment modality, chemotherapy combined with local therapy is the mainstream in dealing with RB, which may maximize the results of eye saving and even vision retaining. New therapeutic techniques including supra-selective ophthalmic artery interventional chemotherapy and intravitreal chemotherapy can further improve the efficacy of treatment, especially the eye salvage rate. The overall level of RB treatment should be improved by promoting the international staging, new therapeutic techniques, and the sequential multiple modality treatment. (Chin J Ophthalmol, 2017, 53: 561 - 565) .

Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.

2009-09-01

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. Onmore » univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.« less

Efficacy of ozone and other treatment modalities for retained placenta in dairy cows.

PubMed

Zobel, R; Tkalčić, S

2013-02-01

Retained placenta is a worldwide recognized clinical condition in puerperal cows, which can significantly affect their health and fertility. Available treatment modalities are often of questionable efficacy or associated with time constraints, practicality or monetary considerations for their wide application in a routine dairy practice. The objective of this study was to compare and assess the efficacy of different treatment options, including a novel ozone treatment, for the retained placenta. Two hundred cows diagnosed with retained placenta were divided into five treatment groups, each receiving a different treatment option. Group A (n = 40) was given a combination treatment of intrauterine ozone and parenteral cephalexin; group B (n = 40) was given intrauterine ozone; group C (n = 40) was given a combination of parenteral cephalexin and intrauterine antibiotic tablets; group D (n = 40) was given only parenteral cephalexin and group E (n = 40) was given parenteral prostaglandins in 11-day intervals. The control group (group Z, n = 200) included cows that gave birth without assistance and were not diagnosed with a retained placenta. The ozone treatment (groups A and B) was found to be the most effective modality resulting in the shortest period of days open, the smallest number of artificial inseminations until pregnancy, the smallest number of animals diagnosed with fever within 10 days post-calving, the highest percentage of animals pregnant within 200 days after calving and the smallest number of animals culled because of infertility, when compared to the other treatment groups. The intrauterine ozone flush therefore has a potential as an efficacious and cost-effective treatment option for retained placenta, with an overall positive effect on puerperal health and fertility in cows. © 2012 Blackwell Verlag GmbH.

A refined surgical treatment modality for bromhidrosis: Subcutaneous scissor with micropore.

PubMed

Dai, Yeqin; Xu, Ai-E; He, Junhua

2017-05-01

Axillary bromhidrosis has a strong negative effect on one's social life. A high success rate and few complications are criteria for a surgical treatment. The objective of this study was to evaluate a new surgical treatment modality for bromhidrosis: subcutaneous scissor with micropore. Twenty patients with bromhidrosis were treated. Patients were placed in a supine position with their treated arms abducted to 110°. After injection of 60 mL of tumescent solution into each axilla, one small incision was made at the middle axillary of the hair-bearing area. The whole hair-bearing skin was undermined at the level of the superficial fat to obtain adequate skin eversion. The flaps were everted to offer full exposure of the apocrine glands, and meticulous excision of each gland was performed. Both sides were punctured with scalpel. The micropore was used for drainage, and whose width was just 3 mm. Finally, the incisions were re-approximated, and bulky compressive dressings were applied to the area for 72 hours. Of the 40 axillae (20 patients), 34 (85.0%) showed excellent results, and six (15.0%) had good results. Malodor was significantly decreased. There were no serious complications. This technique can produce excellent results with a lower complication rate than most other surgical modalities and can be performed without costly equipment. © 2017 Wiley Periodicals, Inc.

The use of Chinese herbal medicine as an adjuvant therapy to reduce incidence of chronic hepatitis in colon cancer patients: A Taiwanese population-based cohort study.

PubMed

Lin, Tsai-Hui; Yen, Hung-Rong; Chiang, Jen-Huai; Sun, Mao-Feng; Chang, Hen-Hong; Huang, Sheng-Teng

2017-04-18

There is a decided lack of in-depth studies to evaluate the effectiveness of Chinese Herbal Medicine (CHM) as an adjuvant therapy on the incidence of chronic hepatitis in patients with colon cancer. The aim of this study is to assess whether CHM treatment decreased the incidence of chronic hepatitis in colon cancer patients who received conventional Western medical treatment. A Taiwanese nationwide population-based study of colon cancer patients receiving Western medicine treatment in conjunction with CHM treatment, using data provided by the National Health Insurance (NHI) Research Database, was conducted. A total of 61676 patients were diagnosed with colon cancer in Taiwan within the defined study period, from 1997 to 2010. After randomly equal matching for age, sex, excluding patients younger than 18 years of age, chronic hepatitis before colon cancer diagnosis date, receiving acupuncture and/or moxibustion and taking CHM for less than 30 days, data from 155 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence of CHM and the therapeutic potential of herbal products in treating patients with colon cancer. CHM used for patients with colon cancer exhibited significantly decreased incidence rates of chronic hepatitis [hazard ratio (HR)=0.53; 95% confidence interval (CI):0.38-0.74], with multivariate adjustment, compared to those without CHM use. The protective effect of CHM treatment with statistical significance across the stratification of age, gender, co-morbidity and treatment modality was noted. The cumulative incidence of chronic hepatitis was also reduced in patients with colon cancer receiving CHM treatment during a five-year period. In this study, we provide the ten most used single herbs and herbal formulas that were prescribed for patients with colon cancer; moreover, we identify the eight single herbs and five formulas used in CHM treatment which significantly decreased incidence of chronic

Pseudofolliculitis barbae: review and update on new treatment modalities.

PubMed

Garcia-Zuazaga, Jorge

2003-07-01

Pseudofolliculits barbae, PFB, is a common cutaneous disease encountered frequently in medical practice. PFB represents a chronic inflammatory condition of the hair follicle caused by ingrown hairs producing an inflammatory foreign body reaction. The pathogenesis of PFB is multifactorial. Factors such as hair type and direction of hair growth play a role in the initial inflammatory reaction. In the armed forces, PFB represents a real challenge for both the physician and the patient. The combat environment, with the recent threat of biological and chemical weapons, requires the servicemen to be clean-shaven for appropriate gas mask fitting around the face. This article will review the etiology, pathogenesis, classification, and newer treatment modalities in the management of PFB.

Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients

PubMed Central

Chandran, Sindhu; Vagefi, Parsia A.

2014-01-01

Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center's experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy. PMID:25349720

Adjuvant whole brain radiotherapy: strong emotions decide but rational studies are needed.

PubMed

Brown, Paul D; Asher, Anthony L; Farace, Elana

2008-04-01

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Paul D.; Asher, Anthony L.; Farace, Elana

2008-04-01

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are stillmore » required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.« less

Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo

PubMed Central

Munks, Michael W.; McKee, Amy S.; MacLeod, Megan K.; Powell, Roger L.; Degen, Jay L.; Reisdorph, Nichole A.; Kappler, John W.

2010-01-01

It has been recognized for nearly 80 years that insoluble aluminum salts are good immunologic adjuvants and that they form long-lived nodules in vivo. Nodule formation has long been presumed to be central for adjuvant activity by providing an antigen depot, but the composition and function of these nodules is poorly understood. We show here that aluminum salt nodules formed within hours of injection and contained the clotting protein fibrinogen. Fibrinogen was critical for nodule formation and required processing to insoluble fibrin by thrombin. DNase treatment partially disrupted the nodules, and the nodules contained histone H3 and citrullinated H3, features consistent with extracellular traps. Although neutrophils were not essential for nodule formation, CD11b+ cells were implicated. Vaccination of fibrinogen-deficient mice resulted in normal CD4 T-cell and antibody responses and enhanced CD8 T-cell responses, indicating that nodules are not required for aluminum's adjuvant effect. Moreover, the ability of aluminum salts to retain antigen in the body, the well-known depot effect, was unaffected by the absence of nodules. We conclude that aluminum adjuvants form fibrin-dependent nodules in vivo, that these nodules have properties of extracellular traps, and the nodules are not required for aluminum salts to act as adjuvants. PMID:20876456

Adjuvant Radiation is Associated with Improved Survival for Select Patients with Non-metastatic Adrenocortical Carcinoma.

PubMed

Nelson, Daniel W; Chang, Shu-Ching; Bandera, Brad C; Fischer, Trevan D; Wollman, Robert; Goldfarb, Melanie

2018-07-01

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy for which surgery is the mainstay of treatment and for which adjuvant radiation is infrequently employed; however, small, single-institution series suggest adjuvant radiation may improve outcomes. All patients with non-metastatic ACC treated with either surgery alone or surgery followed by adjuvant radiation were identified in the 2004-2013 National Cancer Database. Factors associated with receipt of radiation and the impact of adjuvant radiation on survival were determined by multivariable analysis. Of 1184 patients, 171 (14.4%) received adjuvant radiation. Patient demographics were similar between the two groups, but those receiving radiation were more likely to have had positive margins following surgery (37.4 vs. 14.6%; p < 0.001), evidence of vascular invasion (14.0 vs. 5.1%; p = 0.05), and receive concurrent chemotherapy (57.3 vs. 28.8%; p < 0.001). After adjustment for tumor and other treatment factors, only positive margins following surgery was associated with an increased likelihood of receiving adjuvant radiation (odds ratio 3.84, 95% confidence interval [CI] 1.95-7.56). Radiation therapy did not confer a difference in median overall survival in the general cohort. However, for patients with positive margins, adjuvant radiation was associated with a 40% decreased yearly risk of death after adjustment for concurrent chemotherapy (hazard ratio 0.60, 95% CI 0.40-0.92; p = 0.02). This survival advantage was not evident for other traditional high-risk features. Adjuvant radiation appears to decrease the risk of death in ACC patients with positive margins following surgical resection, but only a small percentage are currently receiving radiation. Multidisciplinary treatment with surgery and radiation should be considered for these patients.

A Case of Therapy-Related Acute Myeloid Leukemia Associated with Adjuvant Temozolomide Chemotherapy for Anaplastic Astrocytoma.

PubMed

Kosugi, Kenzo; Saito, Katsuya; Takahashi, Wataru; Tokuda, Yukina; Tomita, Hideyuki

2017-05-01

Temozolomide (TMZ) is now standard adjuvant therapy in combination with radiotherapy for patients with newly diagnosed malignant glioma. Treatment-related myelodysplastic syndrome and acute treatment-related leukemia (t-AML) associated with TMZ chemotherapy for patients with glioma is quite a rare complication. A 43-year-old man with an anaplastic astrocytoma received radiation therapy synchronized with ranimustine and adjuvant TMZ chemotherapy for 15 cycles. Close follow-up magnetic resonance imaging of the head during TMZ chemotherapy showed no evidence of tumor progression. One year after the completion of TMZ chemotherapy, a bone-marrow aspiration was performed because the patient's white blood cell count decreased. He was diagnosed with t-AML based on the bone marrow examination, and then he was referred to the cancer center for the treatment of t-AML. In this case study, we continued adjuvant TMZ therapy beyond the recommended 6 cycles. Currently, there is no consensus as to how long the adjuvant TMZ therapy should be continued for the treatment of residual tumor showing no apparent interval change. A new decision-making tool to assess the clinical benefits against the side effects for long-term adjuvant TMZ therapy is needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Ketamine as an Analgesic Adjuvant in Adult Trauma Intensive Care Unit Patients With Rib Fracture.

PubMed

Walters, Mary K; Farhat, Joseph; Bischoff, James; Foss, Mary; Evans, Cory

2018-03-01

Rib fracture associated pain is difficult to control. There are no published studies that use ketamine as a therapeutic modality to reduce the amount of opioid to control rib fracture pain. To examine the analgesic effects of adjuvant ketamine on pain scale scores in trauma intensive care unit (ICU) rib fracture. This retrospective, case-control cohort chart review evaluated ICU adult patients with a diagnosis of ≥1 rib fracture and an Injury Severity Score >15 during 2016. Patients received standard-of-care pain management with the physician's choice analgesics with or without ketamine as a continuous, fixed, intravenous infusion at 0.1 mg/kg/h. A total of 15 ketamine treatment patients were matched with 15 control standard-of-care patients. Efficacy was measured via Numeric Pain Scale (NPS)/Behavioral Pain Scale (BPS) scores, opioid use, and ICU and hospital length of stay. Safety of ketamine was measured by changes in vital signs, adverse effects, and mortality. Average NPS/BPS, severest NPS/BPS, and opioid use were lower in the ketamine group than in controls (NPS: 4.1 vs 5.8, P < 0.001; severest NPS: 7.0 vs 8.9, P = 0.004; opioid use: 2.5 vs 3.5 mg morphine equivalents/h/d, P = 0.015). No difference was found between the cohort's length of stay or mortality. Average diastolic blood pressure was higher in the treatment group versus the control group (75.3 vs 64.6 mm Hg, P = 0.014). Low-dose ketamine appears to be a safe and effective adjuvant option to reduce pain and decrease opioid use in rib fracture.

Adjuvant treatment may benefit patients with high-risk upper rectal cancer: A nomogram and recursive partitioning analysis of 547 patients.

PubMed

Wang, Xin; Jin, Jing; Yang, Yong; Liu, Wen-Yang; Ren, Hua; Feng, Yan-Ru; Xiao, Qin; Li, Ning; Deng, Lei; Fang, Hui; Jing, Hao; Lu, Ning-Ning; Tang, Yu; Wang, Jian-Yang; Wang, Shu-Lian; Wang, Wei-Hu; Song, Yong-Wen; Liu, Yue-Ping; Li, Ye-Xiong

2016-10-04

The role of adjuvant chemoradiotherapy (ACRT) or adjuvant chemotherapy (ACT) in treating patients with locally advanced upper rectal cancer (URC) after total mesorectal excision (TME) surgery remains unclear. We developed a clinical nomogram and a recursive partitioning analysis (RPA)-based risk stratification system for predicting 5-year cancer-specific survival (CSS) to determine whether these individuals require ACRT or ACT. This retrospective analysis included 547 patients with primary URC. A nomogram was developed based on the Cox regression model. The performance of the model was assessed by concordance index (C-index) and calibration curve in internal validation with bootstrapping. RPA stratified patients into risk groups based on their tumor characteristics. Five independent prognostic factors (age, preoperative increased carcinoembryonic antigen and carcinoma antigen 19-9, positive lymph node [PLN] number, tumor deposit [TD], pathological T classification) were identified and entered into the predictive nomogram. The bootstrap-corrected C-index was 0.757. RPA stratification of the three prognostic groups showed obviously different prognosis. Only the high-risk group (patients with PLN ≤ 6 and TD, or PLN > 6) benefited from ACRT plus ACT when compared with surgery followed by ACRT or ACT, and surgery alone (5-year CSS: 70.8% vs. 57.8% vs. 15.6%, P < 0.001). Our nomogram predicts 5-year CSS after TME surgery for locally advanced rectal cancer and RPA-based stratification indicates that ACRT plus ACT post-surgery may be an important treatment plan with potentially ignificant survival advantages in high-risk URC. This may help to select candidates of adjuvant treatment in prospective studies.

Use and Effectiveness of Adjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer in Men.

PubMed

Venigalla, Sriram; Carmona, Ruben; Guttmann, David M; Jain, Varsha; Freedman, Gary M; Clark, Amy S; Shabason, Jacob E

2018-05-24

Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)-positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. Receipt of adjuvant endocrine therapy. Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. The primary study cohort comprised 10 173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961 676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%, P < .001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63; P < .001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25; P = .02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15; P < .001) or chemotherapy

Current concepts for the combined treatment modality of ionizing radiation with anticancer agents.

PubMed

Oehler, Christoph; Dickinson, Daniel J; Broggini-Tenzer, Angela; Hofstetter, Barbara; Hollenstein, Andreas; Riesterer, Oliver; Vuong, Van; Pruschy, Martin

2007-01-01

In current applied radiobiology, there exists a tremendous effort in basic and translational research to identify novel treatment modalities combining ionizing radiation with anticancer agents. This is mainly due to the highly improved molecular understanding of intrinsic radioresistance and the profiling of cellular stress responses to irradiation during recent years. Ionizing radiation not only damages DNA but also affects multiple cellular components that induce a multi-layered stress response. The treatment responses can be restricted to the individual cell level but might also be part of an intercellular stress communication network. Both DNA damage-induced signaling (which results in cell cycle arrest and induction of the DNA-repair machinery) and also ionizing radiation-induced signal transduction cascades, which are generated at cellular sites distant from and independent of DNA-damage, represent interesting targets for anticancer treatment modalities to sensitize for ionizing radiation. Due to the lack of molecular knowledge classic radiobiology assembled the cellular and tissue responses into four groups (4 R's of radiotherapy) which describe biological factors influencing the treatment response to fractionated radiotherapy. These classic 4 R's are Repair, Reassortment, Repopulation and Reoxygenation. With the tremendous progress in molecular oncology we now begin to understand theses factors on the molecular level. At the same time this classification may guide modern molecular radiobiologists to identify novel pharmaceuticals and antisignaling agents which can modulate the treatment response to irradiation. In this review we describe current approaches to sensitize tumor cells with novel anticancer agents along the lines of these 4 R's.

Carbohydrate-based vaccine adjuvants - discovery and development.

PubMed

Hu, Jing; Qiu, Liying; Wang, Xiaoli; Zou, Xiaopeng; Lu, Mengji; Yin, Jian

2015-10-01

The addition of a suitable adjuvant to a vaccine can generate significant effective adaptive immune responses. There is an urgent need for the development of novel po7tent and safe adjuvants for human vaccines. Carbohydrate molecules are promising adjuvants for human vaccines due to their high biocompatibility and good tolerability in vivo. The present review covers a few promising carbohydrate-based adjuvants, lipopolysaccharide, trehalose-6,6'-dibehenate, QS-21 and inulin as examples, which have been extensively studied in human vaccines in a number of preclinical and clinical studies. The authors discuss the current status, applications and strategies of development of each adjuvant and different adjuvant formulation systems. This information gives insight regarding the exciting prospect in the field of carbohydrate-based adjuvant research. Carbohydrate-based adjuvants are promising candidates as an alternative to the Alum salts for human vaccines development. Furthermore, combining two or more adjuvants in one formulation is one of the effective strategies in adjuvant development. However, further research efforts are needed to study and develop novel adjuvants systems, which can be more stable, potent and safe. The development of synthetic carbohydrate chemistry can improve the study of carbohydrate-based adjuvants.

Aerial spray adjuvants for herbicidal drift control.

Treesearch

Gratkowski H.; Stewart R.

1973-01-01

Increased public concern about pesticides requires that foresters reduce drift and insure precise application of herbicides to the areas requiring treatment. Drift control is necessary near waterways and other ecologically sensitive areas. This publication discusses available drift control adjuvants for herbicidal sprays. These include invert emulsions, thickening...

Exercise for women receiving adjuvant therapy for breast cancer.

PubMed

Furmaniak, Anna C; Menig, Matthias; Markes, Martina H

2016-09-21

A huge clinical research database on adjuvant cancer treatment has verified improvements in breast cancer outcomes such as recurrence and mortality rates. On the other hand, adjuvant and neoadjuvant therapy with chemotherapy and radiotherapy impacts on quality of life due to substantial short- and long-term side effects. A number of studies have evaluated the effect of exercise interventions on those side effects. This is an updated version of the original Cochrane review published in 2006. The original review identified some benefits of physical activity on physical fitness and the resulting capacity for performing activities of daily life. It also identified a lack of evidence for other outcomes, providing clear justification for an updated review. To assess the effect of aerobic or resistance exercise interventions during adjuvant treatment for breast cancer on treatment-related side effects such as physical deterioration, fatigue, diminished quality of life, depression, and cognitive dysfunction. We carried out an updated search in the Cochrane Breast Cancer Group Specialised Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2015), MEDLINE (1966 to 30 March 2015), and EMBASE (1966 to 30 March 2015). We did not update the original searches in CINAHL (1982 to 2004), SPORTDiscus (1975 to 2004), PsycINFO (1872 to 2003), SIGLE (1880 to 2004), and ProQuest Digital Dissertations (1861 to 2004). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 30 March 2015. We screened references in relevant reviews and published clinical trials. We included randomised controlled trials that examined aerobic or resistance exercise or both in women undergoing adjuvant treatment for breast cancer. Published and unpublished trials were eligible. Two review authors independently performed data extraction, assessed trials, and graded the

Regulatory considerations on new adjuvants and delivery systems.

PubMed

Sesardic, D

2006-04-12

New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

Adjuvant chemoradiation for resected gallbladder cancer: Treatment strategies for one of the leading causes of cancer death in Chilean women.

PubMed

Müller, Bettina; Sola, José A; Carcamo, Marcela; Ciudad, Ana M; Trujillo, Cristian; Cerda, Berta

2013-01-01

Gallbladder cancer (GBC) is the second leading cause of cancer death in women in Chile. Even after curative surgery, prognosis is grim. To evaluate acute and late toxicity and efficacy of adjuvant chemoradiation (CRT) after curatively resected GBC. We retrospectively analyzed the cohort of patients diagnosed between January 1999 and December 2009, treated with adjuvant CRT at our institution. Treatment protocol considered external beam radiation (RT) (45-54 Gy) to tumor bed and regional lymph nodes with or without concurrent 5-fluorouracil (5-FU) (500 mg/m2/day by 120-hours continuous infusion on days 1-5 and 29-33). Data was obtained from medical records, mortality from death certificates. Survival was estimated by Kaplan- Meier curves. 46 patients with curatively resected GBC received adjuvant CRT. Median age was 57 years (range 33-76); 39 patients were female. After diagnosis, a second surgery was performed in 42 patients. Cholecystectomy with hepatic segmentectomy and lymphadenectomy was the curative surgery in 41 patients. All patients received RT with a planned dose of 45 Gy in 25 fractions, 11 patients received a boost to the tumor bed up to 54 Gy and 34 patients had concurrent 5-FU. Therapy was well tolerated. Five patients experienced grade 3 toxicities. No grade 4 or 5 toxicity was observed. No grade >2 late toxicity was observed. Three- and 5-year overall survival (OS) were 57% and 51%, respectively. Adjuvant chemoradiation is well tolerated and might impact favorably on survival in patients with curatively resected GBC.

[Recurrence rate following adjuvant strontium-90 brachytherapy after excision of conjunctival melanoma].

PubMed

Krause, L; Ritter, C; Wachtlin, J; Kreusel, K-M; Höcht, S; Foerster, M H; Bechrakis, N E

2008-07-01

Because of the high local recurrence rates after excision of conjunctival melanomas, adjuvant local chemotherapy or irradiation is recommended. Strontium-90 brachytherapy is one radiotherapeutic option due to its low penetration depth. 15 patients with conjunctival melanoma were treated with adjuvant strontium-90 brachytherapy after tumour excision. The treatment was fractionated into 9 irradiation sessions with 6 Gy each. The mean follow-up was 35 months (12-60 months). Seven patients (46%) had no recurrence during the follow-up. Three patients (20%) had a recurrence in the treated or adjacent area. Eight patients (53%) developed new tumours in non-treated areas. Strontium-90 brachytherapy is a useful adjuvant in the treatment of conjunctival melanomas. Regular ophthalmoscopic controls are necessary because of the high rate of new tumours in non-irradiated areas, especially in cases with primary acquired melanosis.

Anomia treatment platform as behavioral engine for use in research on physiological adjuvants to neurorehabilitation.

PubMed

Kendall, Diane; Raymer, Anastasia; Rose, Miranda; Gilbert, JoEllen; Gonzalez Rothi, Leslie J

2014-01-01

The purpose of this study was to create a "behavioral treatment engine" for future use in research on physiological adjuvants in aphasia rehabilitation. We chose the behavioral target anomia, which is a feature displayed by many persons who have aphasia. Further, we wished to saturate the treatment approach with many strategies and cues that have been empirically reported to have a positive influence on aphasia outcome, with the goal being to optimize the potential for positive response in most participants. A single-subject multiple baseline design with replication across eight participants was employed. Four men and four women, with an average age of 62 yr and an average of 63.13 mo poststroke onset, served as participants. Word-retrieval treatment was administered 3 d/wk, 1 h/d for a total of 20 treatment hours (6-7 wk). Positive acquisition effects were evident in all eight participants (d effect size [ES] = 5.40). Treatment effects were maintained 3 mo after treatment termination for five participants (d ES = 2.94). Within and across semantic category, generalization was minimal (d ES = 0.43 within and 1.09 across). This study demonstrates that this behavioral treatment engine provides a solid platform on which to base future studies whereby various treatment conditions are manipulated and pharmacologic support is added.

Adjuvant chemotherapy for endometrial cancer after hysterectomy

PubMed Central

Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

2014-01-01

Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

Retrospective study of the physical therapy modalities applied in head and neck l ymphedema treatment.

PubMed

Tacani, Pascale Mutti; Franceschini, Juliana Pereira; Tacani, Rogério Eduardo; Machado, Aline Fernanda Perez; Montezello, Débora; Góes, João Carlos Guedes Sampaio; Marx, Angela

2016-02-01

Secondary lymphedema after head and neck cancer treatment is a serious complication and its management can be a challenge. The purpose of this study was to verify which physical therapy modalities were applied in the treatment of head and neck lymphedema through a retrospective analysis. A retrospective study was developed, based on the analysis of medical records of 32 patients treated in the physiotherapy outpatient department of the Brazilian Institute of Cancer Control (IBCC). The physiotherapy included manual lymphatic drainage, massage, exercises, patient education, and compression therapy with an average of 23.9 ± 14.8 sessions. Measurement results showed a significant reduction of face and neck lymphedema (p < .05) and pain (from 7.8 ± 2.2 to 3.6 ± 1.6; p < .001). The physical therapy modalities based on strategic manual lymphatic drainage, shoulder girdle massage, facial, tongue and neck exercises, compressive therapy at home, and patient education showed reduction of the lymphedema and pain, both of them secondary to head and neck cancer treatment. © 2014 Wiley Periodicals, Inc.

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.

PubMed

Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida

2012-12-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer

PubMed Central

Wojcieszek, Piotr; Białas, Brygida

2012-01-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years. PMID:23378855

Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

PubMed

El Hage Chehade, Hiba; Wazir, Umar; Mokbel, Kinan; Kasem, Abdul; Mokbel, Kefah

2018-01-01

Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Adjuvant chemotherapy for soft tissue sarcoma.

PubMed

Casali, Paolo G

2015-01-01

Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence.

Characterizing smoking, cessation services, and quit interest across outpatient substance abuse treatment modalities

PubMed Central

McClure, Erin A.; Acquavita, Shauna P.; Dunn, Kelly E.; Stoller, Kenneth B.; Stitzer, Maxine L.

2013-01-01

The majority of individuals seeking treatment for substance use disorders are cigarette smokers, yet smoking cessation is rarely addressed during treatment. Conducting a detailed smoking-related characterization of substance abuse treatment patients across treatment modalities may facilitate the development of tailored treatment strategies. This study administered a battery of self-report instruments to compare tobacco use, quit attempts, smoking knowledge and attitudes, program services, and interest in quitting among smoking patients enrolled in opioid replacement therapy (ORT) vs. non-opioid replacement (non-ORT). ORT compared with non-ORT participants smoked more heavily, had greater tobacco dependence, and endorsed greater exposure to smoking cessation services at their treatment programs. Favorable attitudes towards cessation during treatment were found within both groups. These data identify several potential clinical targets, most notably including confidence in abstaining and attitudes toward cessation pharmacotherapies that may be addressed by substance abuse treatment clinics. PMID:23988192

Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea.

PubMed

Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

2016-11-01

Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP.This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA.Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively.The MAD treatment resulted in a significant reduction in apnea-hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA.These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP.

Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea

PubMed Central

Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

2016-01-01

Abstract Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP. This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA. Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively. The MAD treatment resulted in a significant reduction in apnea–hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA. These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP. PMID:27861349

Treatment trends and survival effects of chemotherapy for hypopharyngeal cancer: Analysis of the National Cancer Data Base.

PubMed

Kuo, Phoebe; Sosa, Julie A; Burtness, Barbara A; Husain, Zain A; Mehra, Saral; Roman, Sanziana A; Yarbrough, Wendell G; Judson, Benjamin L

2016-06-15

The current study was performed to characterize trends and survival outcomes for chemotherapy in the definitive and adjuvant treatment of hypopharyngeal cancer in the United States. A total of 16,248 adult patients diagnosed with primary hypopharyngeal cancer without distant metastases between 1998 and 2011 were identified in the National Cancer Data Base. The association between treatment modality and overall survival was analyzed using Kaplan-Meier survival curves and 5-year survival rates. A multivariate Cox regression analysis was performed on a subset of 3357 cases to determine the treatment modalities that predict improved survival when controlling for demographic and clinical factors. There was a significant increase in the use of chemotherapy with radiotherapy both as definitive treatment (P<.001) and as adjuvant chemoradiotherapy with surgery (P=.001). This was accompanied by a decrease in total laryngectomy/pharyngectomy rates (P<.001). Chemoradiotherapy was associated with improved 5-year survival compared with radiotherapy alone in the definitive setting (31.8% vs 25.2%; log rank P<.001). Similarly, in multivariateanalysis, definitive radiotherapy was found to be associated with compromised survival compared with definitive chemoradiotherapy (hazard ratio, 1.51; P<.001). Survival analysis revealed that overall 5-year survival rates were higher for chemoradiotherapy compared with radiotherapy alone in the definitive setting, but were comparable between surgery with chemoradiotherapy and surgery with radiotherapy. Cancer 2016;122:1853-60. © 2016 American Cancer Society. © 2016 American Cancer Society.

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early Stage HER2-Positive Breast Cancer.

PubMed

Singh, Harpreet; Walker, Amanda J; Amiri-Kordestani, Laleh; Cheng, Joyce; Tang, Shenghui; Balcazar, Pamela; Barnett-Ringgold, Kimberly; Palmby, Todd R; Cao, Xianhua; Zheng, Nan; Liu, Qi; Yu, Jingyu; Pierce, William F; Daniels, Selena R; Sridhara, Rajeshwari; Ibrahim, Amna; Kluetz, Paul G; Blumenthal, Gideon M; Beaver, Julia A; Pazdur, Richard

2018-03-09

On July 17, 2017, the Food and Drug Administration (FDA) approved neratinib (NERLYNX, Puma Biotechnology, Inc) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to neratinib (n=1420) or placebo (n=1420) for one year. The primary endpoint was invasive disease-free survival (iDFS) defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral or contralateral breast cancer), distance recurrence, or death from any cause, with two years and 28 days of follow up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified hazard ratio of 0.66 (95% CI: 0.49, 0.90, p=0.008). Estimated iDFS rate at 2-years was 94.2% (95% CI: 92.6%, 95.4%) in patients treated with neratinib vs. 91.9% (95% CI: 90.2%, 93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE) with a 40% incidence of Grade 3 or 4 diarrhea and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Copyright ©2018, American Association for Cancer Research.

High energy devices versus low energy devices in orthopedics treatment modalities

NASA Astrophysics Data System (ADS)

Schultheiss, Reiner

2003-10-01

The orthopedic consensus group defined in 1997 the 42 most likely relevant parameters of orthopedic shock wave devices. The idea of this approach was to correlate the different clinical outcomes with the physical properties of the different devices with respect to their acoustical waves. Several changes in the hypothesis of the dose effect relationship have been noticed since the first orthopedic treatments. The relation started with the maximum pressure p+, followed by the total energy, the energy density; and finally the single treatment approach using high, and then the multiple treatment method using low energy. Motivated by the reimbursement situation in Germany some manufacturers began to redefine high and low energy devices independent of the treatment modality. The OssaTron as a high energy, single treatment electro hydraulic device gained FDA approval as the first orthopedic ESWT device for plantar fasciitis and, more recently, for lateral epicondylitis. Two low energy devices have now also gained FDA approval based upon a single treatment. Comparing the acoustic data, differences between the OssaTron and the other devices are obvious and will be elaborated upon. Cluster analysis of the outcomes and the acoustical data are presented and new concepts will be suggested.

Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

PubMed

Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.

Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

PubMed Central

Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format. PMID:22505817

Total gastrectomy increases the incidence of grade III and IV toxicities in patients with gastric cancer receiving adjuvant TS-1 treatment.

PubMed

Chou, Wen-Chi; Chang, Chia-Lun; Liu, Keng-Hao; Hsu, Jun-Te; Cheng, Wei Hong; Hsu, Hung-Chih; Shen, Wen-Chi; Hung, Yu-Shin; Chen, Jen-Shi

2013-11-01

We aimed to evaluate the safety and efficacy of TS-1 adjuvant chemotherapy in Taiwanese patients with gastric cancer. We included in this study patients with locally advanced gastric cancer who received adjuvant TS-1 or 5-fluorouracil chemotherapy after curative surgery and extended lymph node dissection between 1 June 2008 and 31 December 2012 at Chang Gung Memorial Hospital. Patient characteristics, tumor features, safety profiles and compliance with TS-1 treatment were retrospectively analyzed from medical charts. Forty patients received adjuvant chemotherapy with TS-1 and 193 with 5-fluorouracil within the study period. The 1- and 2-year overall survival rates were 90.6% and 87% in the TS-1 group and 95.4% and 86.8% in the 5-fluorouracil group (P = 0.34). The 1- and 2-year disease-free survival rates were 90.6% and 74.7% in the TS-1 group and 88% and 75.7% in the 5-fluorouracil group (P = 0.66). In the TS-1 group, tumor recurrence was more frequent in those with >15 metastatic lymph nodes than ≤15. Overall, 78.9%, 74.3%, 62.1% and 56% of patients underwent TS-1 treatment for at least 3, 6, 9 and 12 months, respectively. The most common adverse events of TS-1 were skin hyperpigmentation (55%), diarrhea (27.5%), dizziness (27.5%) and leucopenia (20%). Severe adverse events (SAEs; grade III or IV toxicity) were diarrhea (7.5%), stomatitis (7.5%), leukopenia (5%), vomiting (2.5%), anorexia (2.5%) and dizziness (2.5%). Patients who underwent total gastrectomy had a significantly greater risk of TS-1-related SAEs than patients who underwent subtotal gastrectomy (40% versus 8%, P = 0.014). The incidence of SAEs during TS-1 therapy was more common in Taiwanese patients with gastric cancer who underwent total gastrectomy compared with those who underwent subtotal gastrectomy. Clinicians must be aware of and able to manage these SAEs to maximize patient compliance with adjuvant TS-1.

Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections.

PubMed

Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

2017-01-01

2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus , we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

PubMed Central

Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

2017-01-01

2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound. PMID:28138218

Survival after recurrence in patients with gastric cancer who receive S-1 adjuvant chemotherapy: exploratory analysis of the ACTS-GC trial.

PubMed

Ito, Seiji; Ohashi, Yasuo; Sasako, Mitsuru

2018-04-20

Some patients develop recurrence after curative resection and adjuvant chemotherapy. S-1, an oral fluoropyrimidine, is one of the standard regimens in adjuvant chemotherapy, and is also used in first-line treatment for advanced/metastatic gastric cancer. It is controversial as to whether the same treatment strategy can be applied for patients who develop recurrence after adjuvant chemotherapy and those who did not receive adjuvant chemotherapy. To investigate this issue, we compared the outcomes of patients who developed recurrences after treatment with or without adjuvant chemotherapy using the results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC). Patients who had confirmed recurrence in the ACTS-GC trial were analyzed. We defined 2 independent cohorts. Cohort 1 patients were divided by whether they received adjuvant chemotherapy (adjuvant S-1 group and surgery-only group). Cohort 2 patients were divided by whether they received a regimen including S-1 (IS) or not including S-1 (NIS) after recurrence. A total of 375 patients experienced recurrence (160 in the adjuvant S-1 group and 215 in the surgery-only group). In cohort 1, the median time from recurrence to death (TFRD) was 11.4 months (95% confidence interval [CI], 8.4-13.9) in the adjuvant S-1 group and 11.3 months (95% CI, 9.7-13.1) in the surgery-only group (hazard ratio [HR], 1.05; 95% CI, 0.84-1.31). In cohort 2, 292 patients received chemotherapy after recurrence and were divided into the IS (n = 189) or the NIS group (n = 103). The median TFRD was 13.9 months (95% CI, 12.7-15.6) in the IS group and 8.1 months (95% CI, 6.6-9.7) in the NIS group (HR, 0.59; 95% CI, 0.45-0.76), and there was no significant interaction between the adjuvant S-1 group and surgery-only group. Adjuvant chemotherapy with S-1 prolonged overall survival without influencing the TFRD. The same treatment strategy may be applied for patients who develop recurrence after adjuvant chemotherapy and

Effects of Screening and Systemic Adjuvant Therapy on ER-Specific US Breast Cancer Mortality

PubMed Central

Munoz, Diego; Near, Aimee M.; van Ravesteyn, Nicolien T.; Lee, Sandra J.; Schechter, Clyde B.; Alagoz, Oguzhan; Berry, Donald A.; Burnside, Elizabeth S.; Chang, Yaojen; Chisholm, Gary; de Koning, Harry J.; Ali Ergun, Mehmet; Heijnsdijk, Eveline A. M.; Huang, Hui; Stout, Natasha K.; Sprague, Brian L.; Trentham-Dietz, Amy; Mandelblatt, Jeanne S.

2014-01-01

Background Molecular characterization of breast cancer allows subtype-directed interventions. Estrogen receptor (ER) is the longest-established molecular marker. Methods We used six established population models with ER-specific input parameters on age-specific incidence, disease natural history, mammography characteristics, and treatment effects to quantify the impact of screening and adjuvant therapy on age-adjusted US breast cancer mortality by ER status from 1975 to 2000. Outcomes included stage-shifts and absolute and relative reductions in mortality; sensitivity analyses evaluated the impact of varying screening frequency or accuracy. Results In the year 2000, actual screening and adjuvant treatment reduced breast cancer mortality by a median of 17 per 100000 women (model range = 13–21) and 5 per 100000 women (model range = 3–6) for ER-positive and ER-negative cases, respectively, relative to no screening and no adjuvant treatment. For ER-positive cases, adjuvant treatment made a higher relative contribution to breast cancer mortality reduction than screening, whereas for ER-negative cases the relative contributions were similar for screening and adjuvant treatment. ER-negative cases were less likely to be screen-detected than ER-positive cases (35.1% vs 51.2%), but when screen-detected yielded a greater survival gain (five-year breast cancer survival = 35.6% vs 30.7%). Screening biennially would have captured a lower proportion of mortality reduction than annual screening for ER-negative vs ER-positive cases (model range = 80.2%–87.8% vs 85.7%–96.5%). Conclusion As advances in risk assessment facilitate identification of women with increased risk of ER-negative breast cancer, additional mortality reductions could be realized through more frequent targeted screening, provided these benefits are balanced against screening harms. PMID:25255803

Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beadle, Beth M.; Guadagnolo, B. Ashleigh; Ballo, Matthew T.

2009-04-01

Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) hadmore » sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.« less

Derivation of mean dose tolerances for new fractionation schemes and treatment modalities

NASA Astrophysics Data System (ADS)

Perkó, Zoltán; Bortfeld, Thomas; Hong, Theodore; Wolfgang, John; Unkelbach, Jan

2018-02-01

Avoiding toxicities in radiotherapy requires the knowledge of tolerable organ doses. For new, experimental fractionation schemes (e.g. hypofractionation) these are typically derived from traditional schedules using the biologically effective dose (BED) model. In this report we investigate the difficulties of establishing mean dose tolerances that arise since the mean BED depends on the entire spatial dose distribution, rather than on the dose level alone. A formula has been derived to establish mean physical dose constraints such that they are mean BED equivalent to a reference treatment scheme. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 24 liver cancer patients for whom both proton and photon IMRT treatment plans were available. The results show that the standard BED equation—neglecting the spatial dose distribution—can overestimate mean dose tolerances for hypofractionated treatments by up to 20%. The shape difference between photon and proton dose distributions can cause 30-40% differences in mean physical dose for plans having identical mean BEDs. Converting hypofractionated, 5/15-fraction proton doses to mean BED equivalent photon doses in traditional 35-fraction regimens resulted in up to 10 Gy higher doses than applying the standard BED formula. The dose shape effect should be accounted for to avoid overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. Additionally, tolerances established for one treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions, such as proton therapy. Last, protons may only allow marginal (5-10%) dose escalation if a fraction-size adjusted organ mean dose is constraining instead of a physical dose.

SU-E-T-410: Evaluation of Treatment Modalities for Stereotactic Lung Radiation Therapy: A Phantom Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mohatt, D; Malhotra, H

Purpose: To evaluate and verify the accuracy of alternative treatment modalities for stereotactic lung therapy with end-to-end testing. We compared three dimensional conformal therapy (3DCRT), dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment using 6 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photons. Methods: A QUASAR respiratory motion phantom was utilized with custom ion chamber and gafchromatic EBT2 film inserts. The phantom contained a low density lung medium with a cylindrical polystyrene tumor (35 cc). Pseudo representative structures for various organs at risk (OAR) were created. Allmore » treatment plans were created using Eclipse ver. 11 using the same image and structure sets, and delivered via Varian TrueBeam STx linear accelerator equipped with high definition MLC. Evaluation of plan quality followed ROTG 0813 criterion for conformity index (CI100%), high dose spillage, D2cm, and R50%. Results: All treatment plans met the OAR dose constraints per protocol and could be delivered without any beam hold offs or other interlocks and hence were deemed clinically safe. For equivalent beam energies, target conformity was improved for all modalities when switching to FFF mode. Treatment efficiency increased for VMAT FFF by a factor of 3–4 over IMRT, and up to factor of 7 when compared to 3DCRT. Pass rates were > 97% for all treatment using gamma criteria of 3%, 3mm. Absolute dose at iso-center was verified with ion chamber, and found to be within 2% of the treatment planning system. Conclusion: The higher dose rate associated with FFF not only reduces delivery times, but in most cases enhances plan quality. The one modality with succeeding best results for all RTOG criterions was VMAT 6 MV FFF. This end-to-end testing provides necessary confidence in the entire dose delivery chain for lung SBRT patients.« less

Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

PubMed

Fox, Christopher B

2013-09-01

The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted.

[Modalities in the treatment of obstructive breathing in sleep].

PubMed

Vukčević, Miodrag

2011-01-01

The goals of OSAS therapy are to improve daytime symptoms especially excessive sleepiness, prevent neurocognitve, metabolic and cardiovascular consequences and quality of life in patients with sleep apnea. A variety of therapy exist starting from general measures that include weight reduction, change in life style, postional therapy, oral devices, upper airway surgery and pharmacotherapy. However, CPAP has been demonstrated to be the most important and highly effective therapy in these disorders. CPAP therapy dramatically improves symptoms and decreases cadriovascular and metabolic consequences stoping the occurence of the apneas. Hoewer, not all patients tolerate CPAP especially patients with milder forms of the disease. The individualised approach wich pay attention to different phenotypes and genotype could select patients for selecitively acting treatment modalities such us mandibular advancement devices and electical stimulation of the upper airway muscles.

Topical tranexamic acid as an adjuvant treatment in melasma: Side-by-side comparison clinical study.

PubMed

Chung, Jong Yoon; Lee, Jong Hee; Lee, Joo Heung

2016-08-01

Tranexamic acid (TNA) is a novel therapeutic agent for hyperpigmented skin disorders. The efficacy and safety of topical TNA in patients with melasma has not been heretofore studied. The main objective of this study is to evaluate the efficacy and safety of topical TNA combined with intense pulsed light (IPL) treatment in Asians with melasma. A randomized, split-face (internally controlled) study was conducted in 15 women who received four monthly sessions of IPL to both sides of the face. Topical TNA or vehicle was applied to a randomly assigned side during and after IPL treatment. Patients were followed up for 12 weeks after completing the IPL treatments. Baseline and follow-up melanin index (MI; measured by Mexameter®, Courage and Khazaka, Cologne, Germany) and modified melasma area and severity index (mMASI) scores were determined. Thirteen subjects completed the study without serious adverse events. MI and mMASI decreased significantly from baseline to 12 weeks after the last IPL treatment on the topical TNA side but not on the vehicle side. The efficacy of topical TNA in preventing rebound pigmentation after IPL treatment was also statistically significant. Topical TNA can be considered an effective and safe adjuvant to conventional treatment for melasma.

Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy

PubMed Central

Jang, Hoon; Hong, Kwonho; Choi, Youngsok

2017-01-01

Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients. PMID:28590419

Successful testing and treating of HIV/AIDS in Indonesia depends on the addiction treatment modality.

PubMed

Iskandar, Shelly; de Jong, Cor Aj; Hidayat, Teddy; Siregar, Ike Mp; Achmad, Tri H; van Crevel, Reinout; van der Ven, Andre

2012-01-01

In many settings, people who inject drugs (PWID) have limited access to human immunodeficiency virus (HIV) care which is provided in several hospitals and primary health centers in big cities. Substance abuse treatment (SAT) can be used as the entry-point to HIV programs. The aim of this study is to describe the characteristics of the PWID who had accessed SAT and determine which SAT modality associates significantly with HIV programs. PWID were recruited by respondent-driven sampling in an urban setting in Java, Indonesia and interviewed with the Addiction Severity Index (ASI), Blood-Borne Virus Transmission Risk Assessment Questionnaires, and Knowledge Questionnaire on HIV/AIDS. The information regarding the use of substance abuse treatment and HIV program were based on questions in ASI. Seventy-seven percent of 210 PWID had accessed SAT at least once. PWID who had accessed a SAT modality reported more severe drug problems. The most widely used SAT were opioid substitution (57%) and traditional/faith-based treatment (56%). Accessing substitution treatment (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.5-13.9) or residential drug-free treatment (adjusted OR = 3.7; 95% CI: 1.4-9.7) was significantly associated with HIV testing, whereas accessing substitution treatment (adjusted OR = 3.8; 95% CI: 1.9-7.5) or other medical services (adjusted OR = 3.1; 95% CI: 1.1-8.7) was significantly associated with HIV treatment. There was no significant association between accessing traditional/faith-based treatment and HIV testing and treatment. Efforts should be made to link HIV services with traditional/faith-based treatment to increase the coverage of HIV programs.

Spatial Analysis of Case-Mix and Dialysis Modality Associations

PubMed Central

Phirtskhalaishvili, Tamar; Bayer, Florian; Edet, Stephane; Bongiovanni, Isabelle; Hogan, Julien; Couchoud, Cécile

2016-01-01

♦ Background: Health-care systems must attempt to provide appropriate, high-quality, and economically sustainable care that meets the needs and choices of patients with end-stage renal disease (ESRD). France offers 9 different modalities of dialysis, each characterized by dialysis technique, the extent of professional assistance, and the treatment site. The aim of this study was 1) to describe the various dialysis modalities in France and the patient characteristics associated with each of them, and 2) to analyze their regional patterns to identify possible unexpected associations between case-mixes and dialysis modalities. ♦ Methods: The clinical characteristics of the 37,421 adult patients treated by dialysis were described according to their treatment modality. Agglomerative hierarchical cluster analysis was used to aggregate the regions into clusters according to their use of these modalities and the characteristics of their patients. ♦ Result: The gradient of patient characteristics was similar from home hemodialyis (HD) to in-center HD and from non-assisted automated peritoneal dialysis (APD) to assisted continuous ambulatory peritoneal dialysis (CAPD). Analyzing their spatial distribution, we found differences in the patient case-mix on dialysis across regions but also differences in the health-care provided for them. The classification of the regions into 6 different clusters allowed us to detect some unexpected associations between case-mixes and treatment modalities. ♦ Conclusions: The 9 modalities of treatment available make it theoretically possible to adapt treatment to patients' clinical characteristics and abilities. However, although we found an overall appropriate association of dialysis modalities to the case-mix, major inter-region heterogeneity and the low rate of peritoneal dialysis (PD) and home HD suggest that factors besides patients' clinical conditions impact the choice of dialysis modality. The French organization should now be

Spatial Analysis of Case-Mix and Dialysis Modality Associations.

PubMed

Phirtskhalaishvili, Tamar; Bayer, Florian; Edet, Stephane; Bongiovanni, Isabelle; Hogan, Julien; Couchoud, Cécile

2016-01-01

♦ Health-care systems must attempt to provide appropriate, high-quality, and economically sustainable care that meets the needs and choices of patients with end-stage renal disease (ESRD). France offers 9 different modalities of dialysis, each characterized by dialysis technique, the extent of professional assistance, and the treatment site. The aim of this study was 1) to describe the various dialysis modalities in France and the patient characteristics associated with each of them, and 2) to analyze their regional patterns to identify possible unexpected associations between case-mixes and dialysis modalities. ♦ The clinical characteristics of the 37,421 adult patients treated by dialysis were described according to their treatment modality. Agglomerative hierarchical cluster analysis was used to aggregate the regions into clusters according to their use of these modalities and the characteristics of their patients. ♦ The gradient of patient characteristics was similar from home hemodialyis (HD) to in-center HD and from non-assisted automated peritoneal dialysis (APD) to assisted continuous ambulatory peritoneal dialysis (CAPD). Analyzing their spatial distribution, we found differences in the patient case-mix on dialysis across regions but also differences in the health-care provided for them. The classification of the regions into 6 different clusters allowed us to detect some unexpected associations between case-mixes and treatment modalities. ♦ The 9 modalities of treatment available make it theoretically possible to adapt treatment to patients' clinical characteristics and abilities. However, although we found an overall appropriate association of dialysis modalities to the case-mix, major inter-region heterogeneity and the low rate of peritoneal dialysis (PD) and home HD suggest that factors besides patients' clinical conditions impact the choice of dialysis modality. The French organization should now be evaluated in terms of patients' quality of

Biotechnology approaches to produce potent, self-adjuvanting antigen-adjuvant fusion protein subunit vaccines.

PubMed

Moyle, Peter Michael

Traditional vaccination approaches (e.g. live attenuated or killed microorganisms) are among the most effective means to prevent the spread of infectious diseases. These approaches, nevertheless, have failed to yield successful vaccines against many important pathogens. To overcome this problem, methods have been developed to identify microbial components, against which protective immune responses can be elicited. Subunit antigens identified by these approaches enable the production of defined vaccines, with improved safety profiles. However, they are generally poorly immunogenic, necessitating their administration with potent immunostimulatory adjuvants. Since few safe and effective adjuvants are currently used in vaccines approved for human use, with those available displaying poor potency, or an inability to stimulate the types of immune responses required for vaccines against specific diseases (e.g. cytotoxic lymphocytes (CTLs) to treat cancers), the development of new vaccines will be aided by the availability of characterized platforms of new adjuvants, improving our capacity to rationally select adjuvants for different applications. One such approach, involves the addition of microbial components (pathogen-associated molecular patterns; PAMPs), that can stimulate strong immune responses, into subunit vaccine formulations. The conjugation of PAMPs to subunit antigens provides a means to greatly increase vaccine potency, by targeting immunostimulation and antigen to the same antigen presenting cell. Thus, methods that enable the efficient, and inexpensive production of antigen-adjuvant fusions represent an exciting mean to improve immunity towards subunit antigens. Herein we review four protein-based adjuvants (flagellin, bacterial lipoproteins, the extra domain A of fibronectin (EDA), and heat shock proteins (Hsps)), which can be genetically fused to antigens to enable recombinant production of antigen-adjuvant fusion proteins, with a focus on their

Unraveling Molecular Signatures of Immunostimulatory Adjuvants in the Female Genital Tract through Systems Biology

PubMed Central

Brinkenberg, Ingrid; Samuelson, Emma; Thörn, Karolina; Nielsen, Jens; Harandi, Ali M.

2011-01-01

Sexually transmitted infections (STIs) unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome data determined which signature pathways, processes and networks are shared by or otherwise exclusive to these 2 classes of experimental vaginal adjuvants in the mouse vagina. To our knowledge, this is the first integrated genome-wide transcriptome analysis of the effects of immunomodulatory adjuvants on the female genital tract of a mammal. These results could inform rational development of effective mucosal adjuvants for vaccination against STIs. PMID:21666746

[Adjuvants in modern medicine and veterinary].

PubMed

Kozlov, V G; Ozherelkov, S V; Sanin, A V; Kozhevnikova, T N

2014-01-01

The review is dedicated to immunologic adjuvants--various natural and synthetics substances that are added to vaccines for stimulation of specific immune response, but they do not induce specific response themselves. Critically important is the selection of the correct adjuvants, for which mechanisms of effect on immune system are studied the most. The majority of these mechanisms as well as physical-chemical and biological features of modern adjuvants are analyzed in the review. The problem of safety of adjuvants, types of immune response induced by adjuvants of various nature, excipients that are being verified or already in use in modern medicine and veterinary are also examined.

Multi-Modality Phantom Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huber, Jennifer S.; Peng, Qiyu; Moses, William W.

2009-03-20

Multi-modality imaging has an increasing role in the diagnosis and treatment of a large number of diseases, particularly if both functional and anatomical information are acquired and accurately co-registered. Hence, there is a resulting need for multi modality phantoms in order to validate image co-registration and calibrate the imaging systems. We present our PET-ultrasound phantom development, including PET and ultrasound images of a simple prostate phantom. We use agar and gelatin mixed with a radioactive solution. We also present our development of custom multi-modality phantoms that are compatible with PET, transrectal ultrasound (TRUS), MRI and CT imaging. We describe bothmore » our selection of tissue mimicking materials and phantom construction procedures. These custom PET-TRUS-CT-MRI prostate phantoms use agargelatin radioactive mixtures with additional contrast agents and preservatives. We show multi-modality images of these custom prostate phantoms, as well as discuss phantom construction alternatives. Although we are currently focused on prostate imaging, this phantom development is applicable to many multi-modality imaging applications.« less

Systematic review of treatment modalities for gingival depigmentation: a random-effects poisson regression analysis.

PubMed

Lin, Yi Hung; Tu, Yu Kang; Lu, Chun Tai; Chung, Wen Chen; Huang, Chiung Fang; Huang, Mao Suan; Lu, Hsein Kun

2014-01-01

Repigmentation variably occurs with different treatment methods in patients with gingival pigmentation. A systemic review was conducted of various treatment modalities for eliminating melanin pigmentation of the gingiva, comprising bur abrasion, scalpel surgery, cryosurgery, electrosurgery, gingival grafts, and laser techniques, to compare the recurrence rates (Rrs) of these treatment procedures. Electronic databases, including PubMed, Web of Science, Google, and Medline were comprehensively searched, and manual searches were conducted for studies published from January 1951 to June 2013. After applying inclusion and exclusion criteria, the final list of articles was reviewed in depth to achieve the objectives of this review. A Poisson regression was used to analyze the outcome of depigmentation using the various treatment methods. The systematic review was based on case reports mainly. In total, 61 eligible publications met the defined criteria. The various therapeutic procedures showed variable clinical results with a wide range of Rrs. A random-effects Poisson regression showed that cryosurgery (Rr = 0.32%), electrosurgery (Rr = 0.74%), and laser depigmentation (Rr = 1.16%) yielded superior result, whereas bur abrasion yielded the highest Rr (8.89%). Within the limit of the sampling level, the present evidence-based results show that cryosurgery exhibits the optimal predictability for depigmentation of the gingiva among all procedures examined, followed by electrosurgery and laser techniques. It is possible to treat melanin pigmentation of the gingiva with various methods and prevent repigmentation. Among those treatment modalities, cryosurgery, electrosurgery, and laser surgery appear to be the best choices for treating gingival pigmentation. © 2014 Wiley Periodicals, Inc.

Cold atmospheric plasma, a novel promising anti-cancer treatment modality.

PubMed

Yan, Dayun; Sherman, Jonathan H; Keidar, Michael

2017-02-28

Over the past decade, cold atmospheric plasma (CAP), a near room temperature ionized gas has shown its promising application in cancer therapy. Two CAP devices, namely dielectric barrier discharge and plasma jet, show significantly anti-cancer capacity over dozens of cancer cell lines in vitro and several subcutaneous xenograft tumors in vivo. In contrast to conventional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment modality. Thus far establishing the chemical and molecular mechanism of the anti-cancer capacity of CAP is far from complete. In this review, we provide a comprehensive introduction of the basics of CAP, state of the art research in this field, the primary challenges, and future directions to cancer biologists.

Platelet-rich plasma-an 'Elixir' for treatment of alopecia: personal experience on 117 patients with review of literature.

PubMed

Garg, Suruchi; Manchanda, Shweta

2017-01-01

Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery and dermatology. PRP is a simple, cost-effective and feasible treatment option with high patient satisfaction for hair loss and can be regarded as a valuable adjuvant treatment modality for androgenic alopecia and other types of non-scarring alopecias. Authors have proposed a hair model termed "Golden anchorage with 'molecular locking' of ectodermal and mesenchymal components for survival and integrity of hair follicle (HF)" in this article. Golden anchorage comprises of bulge stem cells, ectodermal basement membrane and bulge portion of APM. PRP with its autologous supply of millions of growth factors works on 'Golden anchorage' along with keratinocytes (PDGF), dermal papilla (IGF and fibroblast growth factor), vasculature (VEGF and PDGF) and neural cells (Nerve Growth Factor) in a multipronged manner serving as an 'elixir' for hair growth and improving overall environment.

Use of implicit persuasion in decision making about adjuvant cancer treatment: A potential barrier to shared decision making.

PubMed

Engelhardt, Ellen G; Pieterse, Arwen H; van der Hout, Anja; de Haes, Hanneke J C J M; Kroep, Judith R; Quarles van Ufford-Mannesse, Patricia; Portielje, Johanneke E A; Smets, Ellen M A; Stiggelbout, Anne M

2016-10-01

Shared decision making (SDM) is widely advocated, especially for preference-sensitive decisions like those on adjuvant treatment for early-stage cancer. Here, decision making involves a subjective trade-off between benefits and side-effects, and therefore, patients' informed preferences should be taken into account. If clinicians consciously or unconsciously steer patients towards the option they think is in their patients' best interest (i.e. implicit persuasion), they may be unwittingly subverting their own efforts to implement SDM. We assessed the frequency of use of implicit persuasion during consultations and whether the use of implicit persuasion was associated with expected treatment benefit and/or decision making. Observational study design in which consecutive consultations about adjuvant systemic therapy with stage I-II breast cancer patients treated at oncology outpatient clinics of general teaching hospitals and university medical centres were audiotaped, transcribed and coded by two researchers independently. In total, 105 patients (median age = 59; range: 35-87 years) were included. A median of five (range: 2-10) implicitly persuasive behaviours were employed per consultation. The number of behaviours used did not differ by disease stage (P = 0.07), but did differ by treatment option presented (P = 0.002) and nodal status (P = 0.01). About 50% of patients with stage I or node-negative disease were steered towards undergoing chemotherapy, whereas 96% of patients were steered towards undergoing endocrine therapy, irrespective of expected treatment benefit. Decisions were less often postponed if more implicit persuasion was used (P = 0.03). Oncologists frequently use implicit persuasion, steering patients towards the treatment option that they think is in their patients' best interest. Expected treatment benefit does not always seem to be the driving force behind implicit persuasion. Awareness of one's use of these steering behaviours

Characteristics and use of treatment modalities of patients with binge-eating disorder in the Department of Veterans Affairs.

PubMed

Bellows, Brandon K; DuVall, Scott L; Kamauu, Aaron W C; Supina, Dylan; Pawaskar, Manjiri; Babcock, Thomas; LaFleur, Joanne

2016-04-01

In 2013 binge-eating disorder (BED) was recognized as a formal diagnosis, but was historically included under the diagnosis code for eating disorder not otherwise specified (EDNOS). This study compared the characteristics and use of treatment modalities in BED patients to those with EDNOS without BED (EDNOS-only) and to matched-patients with no eating disorders (NED). Patients were identified for this study from electronic health records in the Department of Veterans Affairs from 2000 to 2011. Patients with BED were identified using natural language processing and patients with EDNOS-only were identified by ICD-9 code (307.50). First diagnosis defined index date for these groups. NED patients were frequency matched to BED patients up to 4:1, as available, on age, sex, BMI, depression, and index month encounter. Baseline characteristics and use of treatment modalities during the post-index year were compared using t-tests or chi-square tests. There were 593 BED, 1354 EDNOS-only, and 1895 matched-NED patients identified. Only 68 patients with BED had an EDNOS diagnosis. BED patients were younger (48.7 vs. 49.8years, p=0.04), more were male (72.2% vs. 62.8%, p<0.001) and obese (BMI 40.2 vs. 37.0, p<0.001) than EDNOS-only patients. In the follow-up period fewer BED (68.0%) than EDNOS-only patients (87.6%, p<0.001), but more BED than NED patients (51.9%, p<0.001) used at least one treatment modality. The characteristics of BED patients were different from those with EDNOS-only and NED as was their use of treatment modalities. These differences highlight the need for a separate identifier of BED. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physical modalities in chronic pain management.

PubMed

Rakel, Barbara; Barr, John O

2003-09-01

The following conclusions can be made based on review of the evidence: There is limited but positive evidence that select physical modalities are effective in managing chronic pain associated with specific conditions experienced by adults and older individuals. Overall, studies have provided the most support for the modality of therapeutic exercise. Different physical modalities have similar magnitudes of effects on chronic pain. Therefore, selection of the most appropriate physical modality may depend on the desired functional outcome for the patient, the underlying impairment, and the patient's preference or prior experience with the modality. Certain patient characteristics may decrease the effectiveness of physical modalities, as has been seen with TENS. These characteristics include depression, high trait anxiety, a powerful others locus of control, obesity, narcotic use, and neuroticism. The effect on pain by various modalities is generally strongest in the short-term period immediately after the intervention series, but effects can last as long as 1 year after treatment (e.g., with massage). Most research has tested the effect of physical modalities on chronic low back pain and knee OA. The effectiveness of physical modalities for other chronic pain conditions needs to be evaluated more completely. Older and younger adults often experience similar effects on their perception of pain from treatment with physical modalities. Therefore, use of these modalities for chronic pain in older adults is appropriate, but special precautions need to be taken. Practitioners applying physical modalities need formal training that includes the risks and precautions for these modalities. If practitioners lack formal training in the use of physical modalities, or if modality use is not within their scope of practice, it is important to consult with and refer patients to members of the team who have this specialized training. Use of a multidisciplinary approach to chronic pain

Laser vaccine adjuvants

PubMed Central

Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

2014-01-01

Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

Modes of Action for Mucosal Vaccine Adjuvants.

PubMed

Aoshi, Taiki

Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types. Although this adjuvant requirement is mostly the same for parental and mucosal vaccines, the development of mucosal vaccine adjuvants requires the specialized consideration of adapting the adjuvants to characteristic mucosal conditions. This review provides a brief overview of mucosa-associated immune response induction processes, such as antigen uptake and dendritic cell subset-dependent antigen presentation. It also highlights several mucosal vaccine adjuvants from recent reports, particularly focusing on their modes of action.

Breast-cancer adjuvant therapy with zoledronic acid.

PubMed

Coleman, Robert E; Marshall, Helen; Cameron, David; Dodwell, David; Burkinshaw, Roger; Keane, Maccon; Gil, Miguel; Houston, Stephen J; Grieve, Robert J; Barrett-Lee, Peter J; Ritchie, Diana; Pugh, Julia; Gaunt, Claire; Rea, Una; Peterson, Jennifer; Davies, Claire; Hiley, Victoria; Gregory, Walter; Bell, Richard

2011-10-13

Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients. In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed. At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths--243 in the zoledronic acid group and 276 in the control group--were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups. These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.).

Role of Adjuvant Therapy for Node-Negative Lung Cancer Invading the Chest Wall.

PubMed

Gao, Sarah J; Corso, Christopher D; Blasberg, Justin D; Detterbeck, Frank C; Boffa, Daniel J; Decker, Roy H; Kim, Anthony W

2017-03-01

The present study investigated the effect of adjuvant chemotherapy and radiation on survival among patients undergoing chest wall resection for T3N0 non-small cell lung cancer (NSCLC). Patients with T3N0 NSCLC who underwent chest wall resection were identified in the National Cancer Data Base in 2004 to 2012. The cohort was divided into patients who had received adjuvant chemotherapy, radiation therapy, chemoradiation therapy, or no adjuvant treatment. Kaplan-Meier and log-rank tests were used to compare overall survival, and a bootstrapped Cox proportional hazards model was used to determine the significant contributors to survival. A subset analysis was performed with stratification by margin status and tumor size. Of 759 patients identified, 42.0% underwent surgery alone, 23.3% underwent surgery followed by chemotherapy, 22.3% underwent surgery followed by chemoradiation therapy, and 12.3% underwent surgery followed by radiotherapy alone. Tumors > 4 cm benefited from adjuvant chemotherapy and radiation therapy in the multivariable analysis, and those ≤ 4 cm benefited only from adjuvant chemotherapy. The subgroup analysis by margin status identified that margin-positive patients with tumors > 4 cm benefited significantly from either adjuvant chemoradiation therapy or radiation therapy alone. T3N0 NSCLC with chest wall invasion requires unique management compared with other stage IIB tumors. An important determinant of management is tumor size, with tumors ≤ 4 cm benefiting from adjuvant chemotherapy and tumors > 4 cm benefiting from adjuvant chemotherapy if margin negative and adjuvant chemoradiation therapy or radiotherapy if margin positive. Copyright © 2016 Elsevier Inc. All rights reserved.

Hepatic resection with or without adjuvant iodine-131-lipiodol for hepatocellular carcinoma: a comparative analysis.

PubMed

Chua, Terence C; Saxena, Akshat; Chu, Francis; Butler, S Patrick; Quinn, Richard J; Glenn, Derek; Morris, David L

2011-04-01

Resection of hepatocellular carcinoma (HCC) is potentially curative; however, recurrence is common. To date, few or no effective adjuvant therapies have been adequately investigated. This study evaluates the efficacy of adjuvant iodine-131-lipiodol after hepatic resection through the experience of a single-center hepatobiliary service of managing this disease. All patients who underwent hepatic resection for HCC and received adjuvant iodine-131-lipiodol between January 1991 and August 2009 were selected for inclusion into the experimental group. A group composed of patients treated during the same time period without adjuvant iodine-131-lipiodol was identified through the unit's HCC surgery database for comparison. The endpoints of this study were disease-free survival and overall survival. Forty-one patients who received adjuvant iodine-131-lipiodol after hepatic resection were compared with a matched group of 41 patients who underwent hepatic resection only. The median disease-free and overall survival were 24 versus 10 months (P = 0.032) and 104 versus 19 months (P = 0.001) in the experimental and control groups, respectively. Rates of intrahepatic-only recurrences (73 vs. 37%; P = 0.02) and surgical and nonsurgical treatments for recurrences (84 vs. 56%; P = 0.04) were higher in the experimental group compared to the control group. The finding of this study corroborates the current evidence from randomized and nonrandomized trials that adjuvant iodine-131-lipiodol improves disease-free and overall survival in patients with HCC after hepatic resection. The lengthened disease-free survival after adjuvant iodine-131-lipiodol allows for further disease-modifying treatments to improve the overall survival.

Human adjuvant-related syndrome or autoimmune/inflammatory syndrome induced by adjuvants. Where have we come from? Where are we going? A proposal for new diagnostic criteria.

PubMed

Alijotas-Reig, J

2015-09-01

In 1964, Miyoshi reported a series of patients with diverse symptoms after receiving treatment with silicone or paraffin fillers. Miyoshi named this condition 'human adjuvant disease'. Since then, the literature has been flooded with case reports and case series of granulomatous and systemic autoimmune disorders related to vaccines, infection or other adjuvants such as silicone and other biomaterials. A new term -autoimmune/inflammatory syndrome induced by adjuvants--has recently been coined for a process that includes several clinical features previously described by Miyoshi plus other clinical and laboratory parameters related to exposure to diverse external stimuli. Disorders such as siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, sick building syndrome and post-vaccination syndrome have been included in autoimmune/inflammatory syndrome induced by adjuvants. Disorders such as Spanish toxic oil syndrome and Ardystil syndrome could also be included. Furthermore, biomaterials other than silicone should also be considered as triggering factors for these adjuvant-related syndromes. New diagnostic criteria in this field have been proposed. Nevertheless, many of these criteria are too subjective, leading to some patients being diagnosed with chronic fatigue syndrome or other 'central sensitization syndromes'. Diagnostic criteria based only on objective clinical and laboratory data to be further discussed and validated are proposed herein. © The Author(s) 2015.

Adjuvant Vaginal Brachytherapy for Early Stage Endometrial Cancer: A Comprehensive Review

PubMed Central

Harkenrider, Matthew M; Block, Alec M; Alektiar, Kaled M; Gaffney, David K; Jones, Ellen; Klopp, Ann; Viswanathan, Akila N; Small, William

2017-01-01

This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the post-operative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early stage endometrial cancer patients results in very low rates of vaginal recurrence (0–3.1%) with low rates of late toxicity which are primarily vaginal in nature. PORTEC-2 supports that VBT results in non-inferior rates of vaginal recurrence compared to external beam radiotherapy (EBRT) for the treatment of high-intermediate risk patients. VBT as a boost following EBRT, in combination with chemotherapy, and for high-risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians both prefer joint decision-making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multi-disciplinary setting and patients should be counseled properly regarding the risks and benefits of adjuvant therapy. PMID:27260082

Risk of treatment related death and febrile neutropaenia with taxane-based adjuvant chemotherapy for breast cancer in a middle income country outside a clinical trial setting.

PubMed

Phua, Chee Ee; Bustam, Anita Zarina; Yusof, Mastura Md; Saad, Marniza; Yip, Cheng-Har; Taib, Nor Aishah; Ng, Char Hong; Teh, Yew Ching

2012-01-01

The risk of treatment-related death (TRD) and febrile neutropaenia (FN) with adjuvant taxane- based chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage in recent years. This study aims to determine these rates in patients treated in University Malaya Medical Centre (UMMC). Patients who were treated with adjuvant taxane-based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates were then determined retrospectively from medical records. TRD was defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. FN was defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L. A total of 622 patients received adjuvant chemotherapy during this period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4 taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens. The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the patients. The FN rate was 10% and there was no TRD. Adjuvant taxane-based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary prophylactic G-CSF should be considered for patients with any additional risk factor for FN.

Adjuvant effects of saponins on animal immune responses*

PubMed Central

Rajput, Zahid Iqbal; Hu, Song-hua; Xiao, Chen-wen; Arijo, Abdullah G.

2007-01-01

Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed. PMID:17323426

Ego mechanisms of defense are associated with patients' preference of treatment modality independent of psychological distress in end-stage renal disease.

PubMed

Hyphantis, Thomas; Katsoudas, Spiros; Voudiclari, Sonia

2010-03-24

Several parameters mediate the selection of treatment modality in end-stage renal disease (ESRD). The nephrology community suggests that patient preference should be the prime determinant of modality choice. We aimed to test whether ego mechanisms of defense are associated with patients' treatment modality preferences, independent of psychological distress. In 58 eligible ESRD patients who had themselves chosen their treatment modality, we administered the Symptom Distress Checklist-90-R and the Defense Style Questionnaire. Thirty-seven patients (53.4%) had chosen hemodialysis and 21 (46.6%) peritoneal dialysis. Patients who preferred peritoneal dialysis were younger (odds ratio [OR], 0.89; 95% confidence interval [CI]: 0.804-0.988), had received more education (OR, 8.84; 95% CI: 1.301-60.161), and were twice as likely to adopt an adaptive defense style as compared to patients who preferred hemodialysis (57.1% vs 27.0%, respectively; P < 0.033). On the contrary, the latter were more likely to adopt an image-distorting defense style (35.1% vs 14.3%; P = 0.038) and passive-aggressive defenses (OR, 0.73: 95% CI: 0.504-1.006). These results were independent of psychological distress. Our findings indicate that the patient's personality should be taken into account, if we are to better define which modalities are best suited to which patients. Also, physicians should bear in mind passive-aggressive behaviors that warrant attention and intervention in patients who preferred hemodialysis.

Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

2010-03-01

Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

Successful testing and treating of HIV/AIDS in Indonesia depends on the addiction treatment modality

PubMed Central

Iskandar, Shelly; de Jong, Cor AJ; Hidayat, Teddy; Siregar, Ike MP; Achmad, Tri H; van Crevel, Reinout; van der Ven, Andre

2012-01-01

Background In many settings, people who inject drugs (PWID) have limited access to human immunodeficiency virus (HIV) care which is provided in several hospitals and primary health centers in big cities. Substance abuse treatment (SAT) can be used as the entry-point to HIV programs. The aim of this study is to describe the characteristics of the PWID who had accessed SAT and determine which SAT modality associates significantly with HIV programs. Methods PWID were recruited by respondent-driven sampling in an urban setting in Java, Indonesia and interviewed with the Addiction Severity Index (ASI), Blood-Borne Virus Transmission Risk Assessment Questionnaires, and Knowledge Questionnaire on HIV/AIDS. The information regarding the use of substance abuse treatment and HIV program were based on questions in ASI. Results Seventy-seven percent of 210 PWID had accessed SAT at least once. PWID who had accessed a SAT modality reported more severe drug problems. The most widely used SAT were opioid substitution (57%) and traditional/faith-based treatment (56%). Accessing substitution treatment (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.5–13.9) or residential drug-free treatment (adjusted OR = 3.7; 95% CI: 1.4–9.7) was significantly associated with HIV testing, whereas accessing substitution treatment (adjusted OR = 3.8; 95% CI: 1.9–7.5) or other medical services (adjusted OR = 3.1; 95% CI: 1.1–8.7) was significantly associated with HIV treatment. There was no significant association between accessing traditional/faith-based treatment and HIV testing and treatment. Conclusion Efforts should be made to link HIV services with traditional/faith-based treatment to increase the coverage of HIV programs. PMID:23293529

Automated VMAT planning for postoperative adjuvant treatment of advanced gastric cancer.

PubMed

Sharfo, Abdul Wahab M; Stieler, Florian; Kupfer, Oskar; Heijmen, Ben J M; Dirkx, Maarten L P; Breedveld, Sebastiaan; Wenz, Frederik; Lohr, Frank; Boda-Heggemann, Judit; Buergy, Daniel

2018-04-23

Postoperative/adjuvant radiotherapy of advanced gastric cancer involves a large planning target volume (PTV) with multi-concave shapes which presents a challenge for volumetric modulated arc therapy (VMAT) planning. This study investigates the advantages of automated VMAT planning for this site compared to manual VMAT planning by expert planners. For 20 gastric cancer patients in the postoperative/adjuvant setting, dual-arc VMAT plans were generated using fully automated multi-criterial treatment planning (autoVMAT), and compared to manually generated VMAT plans (manVMAT). Both automated and manual plans were created to deliver a median dose of 45 Gy to the PTV using identical planning and segmentation parameters. Plans were evaluated by two expert radiation oncologists for clinical acceptability. AutoVMAT and manVMAT plans were also compared based on dose-volume histogram (DVH) and predicted normal tissue complication probability (NTCP) analysis. Both manVMAT and autoVMAT plans were considered clinically acceptable. Target coverage was similar (manVMAT: 96.6 ± 1.6%, autoVMAT: 97.4 ± 1.0%, p = 0.085). With autoVMAT, median kidney dose was reduced on average by > 25%; (for left kidney from 11.3 ± 2.1 Gy to 8.9 ± 3.5 Gy (p = 0.002); for right kidney from 9.2 ± 2.2 Gy to 6.1 ± 1.3 Gy (p <  0.001)). Median dose to the liver was lower as well (18.8 ± 2.3 Gy vs. 17.1 ± 3.6 Gy, p = 0.048). In addition, Dmax of the spinal cord was significantly reduced (38.3 ± 3.7 Gy vs. 31.6 ± 2.6 Gy, p <  0.001). Substantial improvements in dose conformity and integral dose were achieved with autoVMAT plans (4.2% and 9.1%, respectively; p <  0.001). Due to the better OAR sparing in the autoVMAT plans compared to manVMAT plans, the predicted NTCPs for the left and right kidney and the liver-PTV were significantly reduced by 11.3%, 12.8%, 7%, respectively (p ≤ 0.001). Delivery time and total

Modes of Action for Mucosal Vaccine Adjuvants

PubMed Central

2017-01-01

Abstract Vaccine adjuvants induce innate immune responses and the addition of adjuvants to the vaccine helps to induce protective immunity in the host. Vaccines utilizing live attenuated or killed whole pathogens usually contain endogenous adjuvants, such as bacterial cell wall products and their genomic nucleic acids, which act as pathogen-associated molecular patterns and are sufficient to induce adaptive immune responses. However, purified protein- or antigen-based vaccines, including component or recombinant vaccines, usually lose these endogenous innate immune stimulators, so the addition of an exogenous adjuvant is essential for the success of these vaccine types. Although this adjuvant requirement is mostly the same for parental and mucosal vaccines, the development of mucosal vaccine adjuvants requires the specialized consideration of adapting the adjuvants to characteristic mucosal conditions. This review provides a brief overview of mucosa-associated immune response induction processes, such as antigen uptake and dendritic cell subset-dependent antigen presentation. It also highlights several mucosal vaccine adjuvants from recent reports, particularly focusing on their modes of action. PMID:28436755

Positive effects of an oil adjuvant on efficacy, dissipation and safety of pyrimethanil and boscalid on greenhouse strawberry.

PubMed

Wang, Zhiwei; Wang, Xinquan; Cang, Tao; Zhao, Xueping; Wu, Shenggan; Qi, Peipei; Wang, Xiangyun; Xu, Xiahong; Wang, Qiang

2018-05-21

Methylated vegetable oil adjuvants can enhance initial deposition and decrease the required dosages of pesticides sprayed on plants, so an oil adjuvant mixed with fungicides were used to prevent and control gray mold in greenhouse strawberry. As the persistence and dietary exposure risks from fungicides on strawberries after using adjuvants have not been assessed, the efficacy, dissipation and safety of pyrimethanil and boscalid in the presence and absence of a methylated vegetable oil adjuvant were evaluated. To better describe the actual use of fungicides in greenhouse strawberry, twice repeated application of fungicides were conducted follower by an optimized QuEChERS pre-treatment method. When applied at 60% of their recommended dosages with the adjuvant, the efficacy of pyrimethanil and boscalid for gray mold was similar to that shown by the treatment of 100% fungicides in absence of the adjuvant based on Duncan's Multiple-Range test, and their average residues increased to 89.0% and 89.3%, respectively. The adjuvant enhanced the accumulation effect of pyrimethanil residue by 31.7% after repeated applications, and the half-lives were similar (5.2 and 4.2 d). The adjuvant had comparable accumulation effects (1.75 and 1.83) and similar half-lives (5.4 and 5.5 d) for boscalid. In absence of adjuvant, the risk quotients (RQs) of pyrimethanil (0.41 and 0.33) and boscalid (0.49 and 0.63) after twice applications at pre-harvest interval were lower than 1. Adding the methylated vegetable oil adjuvant to fungicides would result in unprolonging half-life and acceptably low dietary exposure risk on strawberries, but lower dosage of fungicides were used. Copyright © 2018. Published by Elsevier Inc.

Combined treatment modalities for age related macular degeneration.

PubMed

Das, R A; Romano, A; Chiosi, F; Menzione, M; Rinaldi, M

2011-02-01

Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD. Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs). The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease. Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of

Role of Adjuvant Radiotherapy in Granulosa Cell Tumors of the Ovary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hauspy, Jan; Beiner, Mario E.; Harley, Ian

2011-03-01

Purpose: To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. Methods and Materials: The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. Results: A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31more » received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p = .02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p = .004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Conclusion: Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs.« less

Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

PubMed

Hauspy, Jan; Beiner, Mario E; Harley, Ian; Rosen, Barry; Murphy, Joan; Chapman, William; Le, Lisa W; Fyles, Anthony; Levin, Wilfred

2011-03-01

To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Novel minimally invasive multi-modality monitoring modalities in neurocritical care.

PubMed

Al-Mufti, Fawaz; Smith, Brendan; Lander, Megan; Damodara, Nitesh; Nuoman, Rolla; El-Ghanem, Mohammad; Kamal, Naveed; Al-Marsoummi, Sarmad; Alzubaidi, Basim; Nuoaman, Halla; Foreman, Brandon; Amuluru, Krishna; Gandhi, Chirag D

2018-07-15

Elevated intracranial pressure (ICP) following brain injury contributes to poor outcomes for patients, primarily by reducing the caliber of cerebral vasculature, and thereby reducing cerebral blood flow. Careful monitoring of ICP is critical in these patients in order to determine prognosis, implement treatment when ICP becomes elevated, and to judge responsiveness to treatment. Currently, the gold standard for monitoring is invasive pressure transducers, usually an intraventricular monitor, which presents significant risk of infection and hemorrhage. These risks made discovering non-invasive methods for monitoring ICP and cerebral perfusion a priority for researchers. Herein we sought to review recent publications on novel minimally invasive multi-modality monitoring techniques that provide surrogate data on ICP, cerebral oxygenation, metabolism and blood flow. While limitations in various forms preclude them from supplanting the use of invasive monitors, these modalities represent useful screening tools within our armamentarium that may be invaluable when the risks of invasive monitoring outweigh the associated benefits. Copyright © 2018 Elsevier B.V. All rights reserved.

Pressure ulcers: Current understanding and newer modalities of treatment

PubMed Central

Bhattacharya, Surajit; Mishra, R. K.

2015-01-01

This article reviews the mechanism, symptoms, causes, severity, diagnosis, prevention and present recommendations for surgical as well as non-surgical management of pressure ulcers. Particular focus has been placed on the current understandings and the newer modalities for the treatment of pressure ulcers. The paper also covers the role of nutrition and pressure-release devices such as cushions and mattresses as a part of the treatment algorithm for preventing and quick healing process of these wounds. Pressure ulcers develop primarily from pressure and shear; are progressive in nature and most frequently found in bedridden, chair bound or immobile people. They often develop in people who have been hospitalised for a long time generally for a different problem and increase the overall time as well as cost of hospitalisation that have detrimental effects on patient's quality of life. Loss of sensation compounds the problem manifold, and failure of reactive hyperaemia cycle of the pressure prone area remains the most important aetiopathology. Pressure ulcers are largely preventable in nature, and their management depends on their severity. The available literature about severity of pressure ulcers, their classification and medical care protocols have been described in this paper. The present treatment options include various approaches of cleaning the wound, debridement, optimised dressings, role of antibiotics and reconstructive surgery. The newer treatment options such as negative pressure wound therapy, hyperbaric oxygen therapy, cell therapy have been discussed, and the advantages and disadvantages of current and newer methods have also been described. PMID:25991879

Adjuvant chemotherapy and whole abdominal irradiation for gastric carcinoma.

PubMed

Kundel, Yulia; Levitt, Mark L; Oberman, Bernice; Sadezki, Siegal; Tichler, Thomas; Symon, Zvi; Catane, Raphael; Pfeffer, Raphael; Brenner, Baruch

2008-01-01

To analyze the efficacy and toxicity of adjuvant chemotherapy followed by whole abdominal irradiation in the treatment of resectable gastric cancer with positive lymph nodes. Between 1996 and 1999, 10 patients with node-positive gastric cancer underwent complete gross resection and were treated by postoperative chemoradiotherapy. The chemotherapy regimen consisted of 5-fluorouracil, 1000 mg/m2/day as a 96-hr continuous infusion on day 1, and cisplatin, 100 mg/m2 on day 2, every 21 days. Six courses were planned. Radiotherapy was administered 3 weeks after completion of the chemotherapy protocol as a single-fraction dose of 600 cGy in a two-field (anterior and posterior) configuration. Treatment was generally well tolerated, with no treatment-related deaths. However, 9 of the 10 patients died of recurrent disease, with a median survival of 20 months (range, 7-84). Adjuvant chemotherapy with whole abdominal irradiation for gastric cancer is safe and tolerable but has no apparent effect on patient outcome. Studies in larger series are needed to evaluate the role of the approach in this disease.

QS-21: a potent vaccine adjuvant

USDA-ARS?s Scientific Manuscript database

QS-21 is an potent adjuvant derived from the bark of a Chilean tree, Quillaja saponaria. One of the advantages of this adjuvant is that it promotes a balanced humoral and cell-mediaed immune response and can be widely applicable to a variety of vaccines. This adjuvant has used for some veterinary va...

CoVaccine HT™ adjuvant is superior to Freund's adjuvants in eliciting antibodies against the endogenous alarmin HMGB1.

PubMed

Lakhan, Nerissa; Stevens, Natalie E; Diener, Kerrilyn R; Hayball, John D

2016-12-01

Adjuvants are used to enhance the immune response against specific antigens for the production of antibodies, with the choice of adjuvant most critical for poorly immunogenic and self-antigens. This study quantitatively and qualitatively evaluated CoVaccine HT™ and Freund's adjuvants for eliciting therapeutic ovine polyclonal antibodies targeting the endogenous alarmin, high mobility group box-1 (HMGB1). Sheep were immunised with HMGB1 protein in CoVaccine HT™ or Freund's adjuvants, with injection site reactions and antibody titres periodically assessed. The binding affinity of antibodies for HMGB1 and their neutralisation activity was determined in-vitro, with in vivo activity confirmed using a murine model of endotoxemia. Results indicated that CoVaccine HT™ elicited significantly higher antibody tires with stronger affinity and more functional potency than antibodies induced with Freund's adjuvants. These studies provide evidence that CoVaccine HT™ is superior to Freund's adjuvants for the production of antibodies to antigens with low immunogenicity and supports the use of this alternative adjuvant for clinical and experimental use antibodies. Copyright © 2016 Elsevier B.V. All rights reserved.

Adjuvant treatment with the bacterial lysate (OM-85) improves management of atopic dermatitis: A randomized study

PubMed Central

Bodemer, Christine; Guillet, Gerard; Cambazard, Frederic; Boralevi, Franck; Ballarini, Stefania; Milliet, Christian; Bertuccio, Paola; La Vecchia, Carlo; Bach, Jean-François; de Prost, Yves

2017-01-01

Background Environmental factors play a major role on atopic dermatitis (AD) which shows a constant rise in prevalence in western countries over the last decades. The Hygiene Hypothesis suggesting an inverse relationship between incidence of infections and the increase in atopic diseases in these countries, is one of the working hypothesis proposed to explain this trend. Objective This study tested the efficacy and safety of oral administration of the bacterial lysate OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), in the treatment of established AD in children. Methods Children aged 6 months to 7 years, with confirmed AD diagnosis, were randomized in a double-blind, placebo-controlled trial to receive, in addition to conventional treatment with emollients and topical corticosteroids, 3.5mg of the bacterial extract OM-85 or placebo daily for 9 months. The primary end-point was the difference between groups in the occurrence of new flares (NF) during the study period, evaluated by Hazard Ratio (HR) derived from conditional Cox proportional hazard regression models accounting for repeated events. Results Among the 179 randomized children, 170 were analysed, 88 in the OM-85 and 82 in the placebo group. As expected most children in both treatment groups experienced at least 1 NF during the study period (75 (85%) patients in the OM-85 group and 72 (88%) in the placebo group). Patients treated with OM-85 as adjuvant therapy had significantly fewer and delayed NFs (HR of repeated flares = 0.80; 95% confidence interval (CI): 0.67–0.96), also when potential confounding factors, as family history of atopy and corticosteroids use, were taken into account (HR = 0.82; 95% CI: 0.69–0.98). No major side effect was reported, with comparable and good tolerability for OM-85 and placebo. Conclusions Results show an adjuvant therapeutic effect of a well standardized bacterial lysate OM-85 on established AD. PMID:28333952

Adjuvant Endocrine Therapy in Breast Cancer: Evolving Paradigms in Premenopausal Women.

PubMed

Rossi, Lorenzo; Pagani, Olivia

2017-05-01

In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences. The adjuvant treatment planning should always be discussed and agreed in a multidisciplinary context. Tamoxifen remains the standard of care in low-risk patients or in case of intolerance to combined treatment with pharmacological ovarian function suppression or aromatase inhibitors. Combination treatment is indicated in intermediate high-risk disease. The patient should always be considered an active partner in the treatment decision process, to improve treatment motivation and adherence. Finally, the therapeutic choice should take into account drug availability and pharmacoeconomic issues, which unfortunately may prevent, in many low-income countries, the provision of such effective treatments.

[Comparative evaluation of the effectiveness of various treatment modalities for accommodation disorders and acquired progressive myopia].

PubMed

Tarutta, E P; Tarasova, N A

2015-01-01

To evaluate the effectiveness of non-surgical treatment of accommodation disorders and progressive myopia in children. A total of 190 patients (380 eyes) with myopia aged from 6 to 18 years (10.79±0.18 years on average) were enrolled and divided into 9 groups depending on the treatment prescribed. Comparative evaluation of different hardware-based treatment modalities for progressive myopia allowed to work out their optimal combination: "Visotronic", "MACDEL 09", and magnetophoresis of Taufon 4%. Such courses, provided twice a year, were associated with optimization of accommodative response and 1.9-2.8 times reduction of the rate of myopia progression. On the contrary, pleoptic therapy showed a negative effect on accommodative tonus and the rate of progression of acquired myopia. Comparative evaluation of different hardware-based treatment modalities for progressive myopia and accommodation disorders allowed to work out their optimal combination: "Visotronic", "MACDEL 09" and magnetophoresis of Taufon 4%. This treatment, provided twice a year, allows to increase accommodative reserves and volume, improve objective accommodative response, and reduce accommodative hypertonus as well as the rate of myopia progression (1.9-2.8 times over a 1.5-year period). Under pleoptic therapy (specialized software, near field speckles, color pulse therapy, Ambliokor device), both accommodative tonus and the rate of myopia progression increased (1.3-1.5 and 1.6 times correspondingly).

Trimethoprim as Adjuvant Treatment in Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial

PubMed Central

Shibre, Teshome; Alem, Atalay; Abdulahi, Abdulreshid; Araya, Mesfin; Beyero, Teferra; Medhin, Girmay; Deyassa, Negusse; Negash, Alemayehu; Nigatu, Alemayehu; Kebede, Derege

2010-01-01

Various infectious agents, such as Toxoplasma gondii, have been hypothesized to be potentially relevant etiological factors in the onset of some cases of schizophrenia. We conducted a randomized, double-blind, placebo-controlled treatment trial in an attempt to explore the hypothesis that the symptoms of schizophrenia may be related to infection of the central nervous system with toxoplasma gondii. Systematically selected patients with ongoing and at least moderately severe schizophrenia from Butajira, in rural Ethiopia, were randomly allocated to trimethoprim or placebo, which were added on to participants' regular antipsychotic treatments. Trial treatments were given for 6 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess outcome. Ninety-one patients were included in the study, with 80 cases (87.9%) positive for T. gondii immunoglobulin G antibody. Seventy-nine subjects (87.0%) completed the trial. The mean age of subjects was 35.3 (SD = 8.0) years, with a mean duration of illness of 13.2 (SD = 6.7) years. Both treatment groups showed significant reduction in the overall PANSS score with no significant between-group difference. In this sample of patients with chronic schizophrenia, trimethoprim used as adjuvant treatment is not superior to placebo. However, it is not possible to draw firm conclusion regarding the etiological role of toxoplasmosis on schizophrenia based on this study because the timing and the postulated mechanisms through which toxoplasmosis produces schizophrenia are variable. PMID:19193743

Vaccine adjuvants: Why and how.

PubMed

Christensen, Dennis

2016-10-02

Novel vaccine strategies include the so-called subunit vaccines, which encompass only the part of the pathogen to which immune recognition results in protection. The high purity of these vaccines make adverse events less likely, but it also makes the vaccines less immunogenic and therefore potentially less effective. Vaccine adjuvants that increase and modulate the immunogenicity of the vaccine are therefore added to solve this problem. Besides aluminum salts, which have been used in vaccines for 90 years, a number of novel vaccine adjuvants have been included in licensed vaccines over the last 30 years. Increasing insight into immunological mechanisms and how to manipulate them has replaced empirical with rational design of adjuvants, leading to vaccine adjuvants with increased and customized immunogenicity profiles without compromising vaccine safety.

Efficacy of adjuvant chemotherapy after surgery when considered over all cancer types: a synthesis of meta-analyses.

PubMed

Bowater, Russell J; Abdelmalik, Sally M E; Lilford, Richard J

2012-10-01

Despite a large number of clinical trials having been conducted to assess the efficacy of adjuvant chemotherapy after surgery for various cancers, whether it is best to use this treatment remains a generally contentious issue for many common cancers. The purpose of this study was to ascertain whether any general conclusions can be drawn about the efficacy or inefficacy of this treatment within different cancer classifications. Meta-analyses of randomized, controlled trials (RCTs) of adjuvant chemotherapy after surgery were synthesized over as many types of cancer as possible. Data sources were Medline, Embase, and the Cochrane library. Eligible meta-analyses were meta-analyses of RCTs for any type of cancer that compared surgery followed by adjuvant chemotherapy with surgery followed by no adjuvant chemotherapy. The literature search found 25 meta-analyses for 15 cancer types that satisfied the criteria necessary for detailed analysis within this study. The estimates of relative risk for all cause mortality were reported as being less than one (indicating adjuvant chemotherapy is beneficial) by all meta-analyses apart from a meta-analysis for colorectal cancer metastasized to the liver. Moreover, 15 of these meta-analyses also reported that the 95% confidence interval for this relative risk is less than one (indicating statistical significance at the 5% level). The results for all cancer types included in this study except for cancer metastasized to the liver can be thought of as supporting each other through the idea of there being a common treatment effect or at least a common range of effect across all (or most) of these cancer types. For example, with regard to cancer types where the evidence in favor of adjuvant chemotherapy after surgery is only moderately strong, the results of this study may encourage more clinicians to regard the use of this treatment as standard practice.

Antibody production in rabbits administered Freund's complete adjuvant and carprofen concurrently.

PubMed

Fishback, Joanna E; Stronsky, Sabrina M; Green, Catherine A; Bean, Krystal D; Froude, Jeffrey W

2016-02-01

Freund's complete adjuvant (FCA) is a commonly used immunopotentiator that can boost polyclonal antibody production in animal models such as rabbits, but FCA is also known to cause inflammation and pain. It is important to balance the welfare of animals with the goal of efficiently producing antibodies, but little is known about how common treatments for pain and inflammation, such as non-steroidal anti-inflammatory drugs (NSAIDs), affect the production of polyclonal antibodies. The purpose of this study was to measure polyclonal antibody production in rabbits that were administered FCA either with or without a concurrent treatment of a NSAID, carprofen. Rabbits were divided into two groups and were administered identical treatments of an antigen with adjuvant, and the treatment group also received carprofen injections at different stages of the study. Carprofen treatment did not significantly affect polyclonal antibody production, which suggests that carprofen and other NSAIDs can be used alongside FCA in rabbits to achieve desired levels of antibody production while minimizing pain and distress associated with the use of FCA.

Rational design of small molecules as vaccine adjuvants.

PubMed

Wu, Tom Y-H; Singh, Manmohan; Miller, Andrew T; De Gregorio, Ennio; Doro, Francesco; D'Oro, Ugo; Skibinski, David A G; Mbow, M Lamine; Bufali, Simone; Herman, Ann E; Cortez, Alex; Li, Yongkai; Nayak, Bishnu P; Tritto, Elaine; Filippi, Christophe M; Otten, Gillis R; Brito, Luis A; Monaci, Elisabetta; Li, Chun; Aprea, Susanna; Valentini, Sara; Calabrό, Samuele; Laera, Donatello; Brunelli, Brunella; Caproni, Elena; Malyala, Padma; Panchal, Rekha G; Warren, Travis K; Bavari, Sina; O'Hagan, Derek T; Cooke, Michael P; Valiante, Nicholas M

2014-11-19

Adjuvants increase vaccine potency largely by activating innate immunity and promoting inflammation. Limiting the side effects of this inflammation is a major hurdle for adjuvant use in vaccines for humans. It has been difficult to improve on adjuvant safety because of a poor understanding of adjuvant mechanism and the empirical nature of adjuvant discovery and development historically. We describe new principles for the rational optimization of small-molecule immune potentiators (SMIPs) targeting Toll-like receptor 7 as adjuvants with a predicted increase in their therapeutic indices. Unlike traditional drugs, SMIP-based adjuvants need to have limited bioavailability and remain localized for optimal efficacy. These features also lead to temporally and spatially restricted inflammation that should decrease side effects. Through medicinal and formulation chemistry and extensive immunopharmacology, we show that in vivo potency can be increased with little to no systemic exposure, localized innate immune activation and short in vivo residence times of SMIP-based adjuvants. This work provides a systematic and generalizable approach to engineering small molecules for use as vaccine adjuvants. Copyright © 2014, American Association for the Advancement of Science.

Adjuvant treatment in patients at high risk of recurrence of thymoma: efficacy and safety of a three-dimensional conformal radiation therapy regimen.

PubMed

Perri, Francesco; Pisconti, Salvatore; Conson, Manuel; Pacelli, Roberto; Della Vittoria Scarpati, Giuseppina; Gnoni, Antonio; D'Aniello, Carmine; Cavaliere, Carla; Licchetta, Antonella; Cella, Laura; Giuliano, Mario; Schiavone, Concetta; Falivene, Sara; Di Lorenzo, Giuseppe; Buonerba, Carlo; Ravo, Vincenzo; Muto, Paolo

2015-01-01

The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma.

Liposomal adjuvants for human vaccines.

PubMed

Alving, Carl R; Beck, Zoltan; Matyas, Gary R; Rao, Mangala

2016-06-01

Liposomes are well-known as drug carriers, and are now critical components of two of six types of adjuvants present in licensed vaccines. The liposomal vaccine adjuvant field has long been dynamic and innovative, and research in this area is further examined as new commercial products appear in parallel with new vaccines. In an arena where successful products exist the potential for new types of vaccines with liposomal adjuvants, and alternative liposomal adjuvants that could emerge for new types of vaccines, are discussed. Major areas include: virosomes, constructed from phospholipids and proteins from influenza virus particles; liposomes containing natural and synthetic neutral or anionic phospholipids, cholesterol, natural or synthetic monophosphoryl lipid A, and QS21 saponin; non-phospholipid cationic liposomes; and combinations and mixtures of liposomes and immunostimulating ingredients as adjuvants for experimental vaccines. Liposomes containing monophosphoryl lipid A and QS21 have considerable momentum that will result soon in emergence of prophylactic vaccines to malaria and shingles, and possible novel cancer vaccines. The licensed virosome vaccines to influenza and hepatitis A will be replaced with virosome vaccines to other infectious diseases. Alternative liposomal formulations are likely to emerge for difficult diseases such as tuberculosis or HIV-1 infection.

Continuous monitoring of arthritis in animal models using optical imaging modalities

NASA Astrophysics Data System (ADS)

Son, Taeyoon; Yoon, Hyung-Ju; Lee, Saseong; Jang, Won Seuk; Jung, Byungjo; Kim, Wan-Uk

2014-10-01

Given the several difficulties associated with histology, including difficulty in continuous monitoring, this study aimed to investigate the feasibility of optical imaging modalities-cross-polarization color (CPC) imaging, erythema index (EI) imaging, and laser speckle contrast (LSC) imaging-for continuous evaluation and monitoring of arthritis in animal models. C57BL/6 mice, used for the evaluation of arthritis, were divided into three groups: arthritic mice group (AMG), positive control mice group (PCMG), and negative control mice group (NCMG). Complete Freund's adjuvant, mineral oil, and saline were injected into the footpad for AMG, PCMG, and NCMG, respectively. LSC and CPC images were acquired from 0 through 144 h after injection for all groups. EI images were calculated from CPC images. Variations in feet area, EI, and speckle index for each mice group over time were calculated for quantitative evaluation of arthritis. Histological examinations were performed, and the results were found to be consistent with those from optical imaging analysis. Thus, optical imaging modalities may be successfully applied for continuous evaluation and monitoring of arthritis in animal models.

Lymphadenectomy and Adjuvant Therapy Improve Survival with Uterine Carcinosarcoma: A Large Retrospective Cohort Study.

PubMed

Versluis, Marco A C; Pielsticker, Cindy; van der Aa, Maaike A; de Bruyn, Marco; Hollema, Harry; Nijman, Hans W

2018-05-23

Uterine carcinosarcoma is a rare, aggressive subtype of endometrial cancer. Treatment consists of hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy (LND). The survival benefit of LND in relation to adjuvant radio- and/or chemotherapy is unclear. We evaluated the impact of LND on survival in relation to adjuvant therapy in uterine carcinosarcoma. Retrospective data on 1,140 cases were combined from the Netherlands Cancer Registry (NCR) and the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). LND was defined as the removal of any nodes. Additionally, cases where 10 nodes or less (LND ≤10) or more than 10 nodes (LND > 10) were removed were analyzed separately. Adjuvant therapy was evaluated as radiotherapy, chemotherapy, or radiochemotherapy. Associations were analyzed by χ2 test, log-rank test, and Cox regression analysis. Overall survival (OS) had improved after total abdominal hysterectomy with bilateral salpingo-oophorectomy with LND > 10 (HR 0.62, 95% CI 0.47-0.83). Adjuvant therapy was related to OS with an HR of 0.64 (95% CI 0.54-0.75) for radiotherapy, an HR of 0.65 (95% CI 0.48-0.88) for chemotherapy, and an HR of 0.25 (95% CI 0.13-0.46) for radiochemotherapy. Additionally, adjuvant treatment was related to OS when lymph nodes were positive (HR 0.22, 95% CI 0.11-0.42), but not when they were negative. LND is related to improved survival when more than 10 nodes are removed. Adjuvant therapy improves survival when LND is omitted, or when nodes are positive. © 2018 S. Karger AG, Basel.

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horowitz, David P.; Hsu, Charles C.; Wang Jingya

2011-08-01

Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients {>=}75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age {>=}75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were {>=}75 years of age and 489 of 655 patients (74.7%) were <75 years of age.more » Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.« less

Platelet-rich plasma—an ‘Elixir’ for treatment of alopecia: personal experience on 117 patients with review of literature

PubMed Central

Manchanda, Shweta

2017-01-01

Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery and dermatology. PRP is a simple, cost-effective and feasible treatment option with high patient satisfaction for hair loss and can be regarded as a valuable adjuvant treatment modality for androgenic alopecia and other types of non-scarring alopecias. Authors have proposed a hair model termed “Golden anchorage with ‘molecular locking’ of ectodermal and mesenchymal components for survival and integrity of hair follicle (HF)” in this article. Golden anchorage comprises of bulge stem cells, ectodermal basement membrane and bulge portion of APM. PRP with its autologous supply of millions of growth factors works on ‘Golden anchorage’ along with keratinocytes (PDGF), dermal papilla (IGF and fibroblast growth factor), vasculature (VEGF and PDGF) and neural cells (Nerve Growth Factor) in a multipronged manner serving as an ‘elixir’ for hair growth and improving overall environment. PMID:28815175

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Longitudinal Assessments of Quality of Life in Endometrial Cancer Patients: Effect of Surgical Approach and Adjuvant Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Le, Tien, E-mail: tle@ottawahospital.on.c; Menard, Chantal; Samant, Rajiv

2009-11-01

Purpose: Adjuvant radiotherapy (RT) is often considered for endometrial cancer. We studied the effect of RT and surgical treatment on patients' quality of life (QOL). Methods and Materials: All patients referred to the gynecologic oncology clinics with biopsy findings showing endometrial cancer were recruited. QOL assessments were performed using the European Organization for Research and Treatment of Cancer QOL questionnaire-C30, version 3. Assessments were obtained at study entry and at regular 3-month intervals for a maximum of 2 years. Open-ended telephone interviews were done every 6 months. Linear mixed regression models were built using QOL domain scores as dependent variables,more » with the predictors of surgical treatment and adjuvant RT type. Results: A total of 40 patients were recruited; 80% of the surgeries were performed by laparotomy. Significant improvements were seen in most QOL domains with increased time from treatment. Adjuvant RT resulted in significantly more severe bowel symptoms and improvement in insomnia compared with conservative follow-up. No significant adverse effect from adjuvant RT was seen on the overall QOL. Bowel symptoms were significantly increased in patients treated with laparotomy compared with laparoscopy in the patients treated with whole pelvic RT. Qualitatively, about one-half of the patients noted improvements in their overall QOL during follow-up, with easy fatigability the most prevalent. Conclusion: No significant adverse effect was seen on patients' overall QOL with adjuvant pelvic RT after the recovery period. The acute adverse effects on patients' QOL significantly improved with an increasing interval from diagnosis.« less

Differences in Funding Sources of Phase III Oncology Clinical Trials by Treatment Modality and Cancer Type.

PubMed

Jairam, Vikram; Yu, James B; Aneja, Sanjay; Wilson, Lynn D; Lloyd, Shane

2017-06-01

Given the limited resources available to conduct clinical trials, it is important to understand how trial sponsorship differs among different therapeutic modalities and cancer types and to consider the ramifications of these differences. We searched clinicaltrials.gov for a cross-sectional register of active, phase III, randomized controlled trials (RCTs) studying treatment-related endpoints such as survival and recurrence for the 24 most prevalent malignancies. We classified the RCTs into 7 categories of therapeutic modality: (1) chemotherapy/other cancer-directed drugs, (2) targeted therapy, (3) surgery, (4) radiation therapy (RT), (5) RT with other modalities, (6) multimodality therapy without RT, and (7) other. RCTs were categorized as being funded by one or more of the following groups: (1) government, (2) hospital/university, (3) industry, and (4) other. χ analysis was performed to detect differences in funding source distribution between modalities and cancer types. The percentage of multimodality trials (5%) and radiation RCTs (4%) funded by industry was less than that for chemotherapy (32%, P<0.01) or targeted therapy (48%, P<0.01). Trials studying targeted therapy were less likely to have hospital/university funding than any of the other modalities (P<0.01 in each comparison). Trials of chemotherapy were more likely to be funded by industry if they also studied targeted therapy (P<0.01). RCTs studying targeted therapies are more likely to be funded by industry than trials studying multimodality therapy or radiation. The impact of industry funding versus institutional or governmental sources of funding for cancer research is unclear and requires further study.

Evaluation and economic impact analysis of different treatment options for ankle distortions in occupational accidents.

PubMed

Audenaert, Amaryllis; Prims, Jente; Reniers, Genserik L L; Weyns, Dirk; Mahieu, Peter; Audenaert, Emmanuel

2010-10-01

Appropriate use of diagnostic and treatment modalities are essential for rational use of resources. The aim of this study is to evaluate the use of diagnostic modalities and different treatment options and their economic impacts following an acute ankle distortion resulting from an occupational accident. We evaluated the type-of-treatment impact on the victims' course of recovery as well as its impact on the associated accident costs. Research was carried out in Belgium. An ankle distortion victims' database consisting of 200 cases of (Belgian) occupational accidents during the period 2005-2007 was analysed. Patients who were prescribed immobilization or the use of adjuvant support or physical therapy (118 cases) were not employed during a period of 37 days on average, with a mean total cost of 3140.14 Euros caused by the ankle sprain. Patients without any adjuvant therapy (82 cases) were characterized by an unemployment rate of 15 days on average, and a total cost of 1077.86 Euros. Cast immobilization, although its application is not supported by evidence-based literature, was still applied in 36% of the population studied and resulted in the longest average absence of work of 42 days with an obvious significant increase in medical and total costs. Our results show a high rate of inappropriate use of cast immobilizations for ankle distortions. From an economic point of view and for the same clinical endpoint (being full resumption of the occupational activities), simple conventional treatment, consisting of rest, ice, compression and elevation at diagnosis with allowance of early weight bearing in the further clinical course, leads to the quickest full resumption of activities in combination with the lowest medical costs, if compared with any other kind of treatment. © 2010 Blackwell Publishing Ltd.

Long term effects of extended adjuvant endocrine therapy on quality of life in breast cancer patients.

PubMed

Kool, M; Fontein, D B Y; Meershoek-Klein Kranenbarg, E; Nortier, J W R; Rutgers, E J T; Marang-van de Mheen, P J; van de Velde, C J H

2015-06-01

The standard treatment for hormone-receptor positive, postmenopausal early breast cancer patients is 5 years of adjuvant endocrine therapy. Previous studies demonstrate that prolonging adjuvant endocrine therapy may improve disease-free survival. However, endocrine therapy is known for its adverse events, which may negatively affect Quality of Life (QoL). The aim of this study is to assess the impact of extended adjuvant endocrine therapy on long-term QoL outcomes. 471 patients selected from the IDEAL trial were invited to complete a questionnaire 1-1.5 years after starting with extended therapy. The questionnaire consisted of the EORTC QLQ-C30 and QLQ-BR23 questionnaires. Mean QoL outcomes were compared with EORTC reference values for stage I and II breast cancer patients and the general population. Furthermore, QoL outcomes were compared between different treatment regimens. A difference of eight points was considered clinically relevant. IDEAL patients receiving extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with reference values for stage I and II breast cancer patients (79.6 versus 64.6; p < 0.01) and the general population (79.6 versus 71.2; p < 0.01). Similar results were found for emotional function, pain, appetite loss, diarrhea and financial problems. Between treatment regimens prior to extended adjuvant endocrine therapy, differences were only found on specific QoL domains (e.g. arm symptoms). Breast cancer patients on extended adjuvant endocrine therapy have significantly and clinically relevant better global QoL compared with other stage I-II breast cancer patients and the general population, 6-8.5 years after diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Controversies in breast cancer: adjuvant and neoadjuvant therapy.

PubMed

Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

2005-06-01

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

Evaluation of the treatment modalities for neurosensory disturbances of the inferior alveolar nerve following retromolar bone harvesting for bone augmentation.

PubMed

Nogami, Shinnosuke; Yamauchi, Kensuke; Shiiba, Shunji; Kataoka, Yoshihiro; Hirayama, Bunichi; Takahashi, Tetsu

2015-03-01

The purpose of this study was to evaluate the treatment modalities for neurosensory disturbances (NSDs) of the inferior alveolar nerve occurring after retromolar bone harvesting for bone augmentation procedures before implant placement. One hundred four patients, of which 49 and 55 exhibited vertical or horizontal alveolar ridge defects in the mandible and maxilla, respectively, were enrolled. Nineteen patients underwent block bone grafting, 38 underwent guided bone generation or autogenous bone grafting combined with titanium mesh reconstruction, and 47 underwent sinus floor augmentation. Using a visual analog scale, we examined subjective symptoms and discomfort related to sensory alteration within the area of the NSDs in these patients. NSDs were clinically investigated using a two-point discrimination test with blunt-tipped calipers. In addition, neurometry was used for evaluation of trigeminal nerve injury. We tested three treatment modalities for NSDs: follow-up observation (no treatment), medication, and stellate ganglion block (SGB). A week after surgery, 26 patients (25.0%) experienced NSDs. Five patients received no treatment, 10 patients received medication, and 11 patients received SGB. Three months after surgery, patients in the medication and SGB group achieved complete recovery. Current perception threshold values recovered to near-baseline values at 3 months: recovery was much earlier in this group than in the other two groups. SGB can accelerate recovery from NSDs. Our results justify SGB as a reasonable treatment modality for NSDs occurring after the harvesting of retromolar bone grafts. Wiley Periodicals, Inc.

Adjuvants: Classification, Modus Operandi, and Licensing.

PubMed

Apostólico, Juliana de Souza; Lunardelli, Victória Alves Santos; Coirada, Fernanda Caroline; Boscardin, Silvia Beatriz; Rosa, Daniela Santoro

2016-01-01

Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations.

Methods to Prepare Aluminum Salt-Adjuvanted Vaccines.

PubMed

Thakkar, Sachin G; Cui, Zhengrong

2017-01-01

Many human vaccines contain certain insoluble aluminum salts such as aluminum oxyhydroxide and aluminum hydroxyphosphate as vaccine adjuvants to boost the immunogenicity of the vaccines. Aluminum salts have been used as vaccine adjuvants for decades and have an established, favorable safety profile. However, preparing aluminum salts and aluminum salt-adjuvanted vaccines in a consistent manner remains challenging. This chapter discusses methods to prepare aluminum salts and aluminum salt-adjuvanted vaccines, factors to consider during preparation, and methods to characterize the vaccines after preparation.

From discovery to licensure, the Adjuvant System story.

PubMed

Garçon, Nathalie; Di Pasquale, Alberta

2017-01-02

Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines.

Applications of nanomaterials as vaccine adjuvants

PubMed Central

Zhu, Motao; Wang, Rongfu; Nie, Guangjun

2014-01-01

Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

Treatment outcome and patterns of relapse following adjuvant carboplatin for stage I testicular seminomatous germ-cell tumour: results from a 17-year UK experience.

PubMed

Chau, C; Cathomas, R; Wheater, M; Klingbiel, D; Fehr, M; Bennett, J; Markham, H; Lee, C; Crabb, S J; Geldart, T

2015-09-01

Following inguinal orchidectomy, management options for patients with stage I seminoma include initial surveillance or treatment with adjuvant radiotherapy or chemotherapy. The anticipated relapse rate for patients followed by surveillance alone is ∼15%, with adjuvant treatment this risk is reduced to ∼4%-5% at 5 years. After carboplatin treatment, follow-up strategies vary and there are no validated, predictive markers of relapse. We conducted a retrospective analysis of all patients presenting with stage I seminoma who received a single cycle of adjuvant carboplatin in South Central England between 1996 and 2013. We report on outcome and the results of univariate and multivariate analysis evaluating possible risk factors for post carboplatin relapse. A total of 517 eligible patients were identified. All underwent nuclear medicine estimation of glomerular filtration rate before treatment with carboplatin (dosed at area under the curve × 7). With a median follow-up of 47.2 months (range 0.4-214 months), 21/517 patients have relapsed resulting in a 5-year estimated relapse-free survival of 95.0% (95% confidence interval 92.8% to 97.3%). Median time to relapse was 22.7 months (range 12.5-109.5 months). Relapse beyond 3 years was rare (4/517; 0.8%). Twenty of 21 (95%) relapsed patients had retroperitoneal lymph node metastases. The majority (16/21; 76%) of patients had elevated tumour markers at relapse. Twenty of 517 (3.9%) patients developed a new contralateral testicular germ-cell cancer. There were no seminoma-related deaths. Tumour size was the only variable significantly associated with an increased risk of relapse. Overall results for this large cohort of patients confirm an excellent prognosis for these patients with outcomes equivalent to those seen in prospective clinical trials. Increasing tumour size alone appears to be associated with an increased risk of post chemotherapy relapse. © The Author 2015. Published by Oxford University Press on behalf of

Micro/nanoparticle adjuvants for antileishmanial vaccines: present and future trends.

PubMed

Badiee, Ali; Heravi Shargh, Vahid; Khamesipour, Ali; Jaafari, Mahmoud Reza

2013-01-21

Leishmania infection continues to have a major impact on public health inducing significant morbidity and mortality mostly in the poorest populations. Drug resistance, toxicity and side effects associated with expensive chemotherapeutic treatments and difficult reservoir control emphasize the need for a safe and effective vaccine which is not available yet. Although, Leishmanization (LZ) was shown to be effective against cutaneous leishmaniasis, standardization and safety are the main problems of LZ. First generation killed parasites demonstrated limited efficacy in phase 3 trials and moreover well defined molecules have not reached to phase 3 yet. Limited efficacy in vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Hence, the use of particulate delivery systems as carriers for antigen and/or immunostimulatory adjuvants for effective delivery to the antigen-presenting cells (APCs) is a valuable strategy to enhance vaccine efficacies. Particle-based delivery systems such as emulsions, liposomes, virosomes, and polymeric microspheres have the potential for successfully delivering antigens, which can then be further improved via incorporation of additional antigenic or immustimulatory adjuvant components in or onto the particle carrier system. In this review, we have attempted to provide a list of particulate vaccine delivery systems involved in the production of candidate leishmaniasis vaccines and introduced some potentially useful vaccine delivery systems for leishmaniasis in future experiments. In conclusion, combination vaccines (adjuvant systems) composed of candidate antigens and more importantly well-developed particulate delivery systems, such as lipid-based particles containing immunostimulatory adjuvants, have a chance to succeed as antileishmanial vaccines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

PubMed Central

Winter-Roach, Brett A; Kitchener, Henry C; Lawrie, Theresa A

2014-01-01

Background Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined. Objectives To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly to determine if clinical subgroups of differing prognosis based on histological sub-type, or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery. Search methods We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH). Selection criteria We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures. Data collection and analysis Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses. Main results Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four

The impact of size on particulate vaccine adjuvants.

PubMed

Shah, Ruchi R; O'Hagan, Derek T; Amiji, Mansoor M; Brito, Luis A

2014-12-01

Particulate adjuvants have been successful at inducing increased immune responses against many poorly immunogenic antigens. However, the mechanism of action of these adjuvants often remains unclear. As more potential vaccine targets are emerging, it is becoming necessary to broaden our knowledge on the factors involved in generating potent immune responses to recombinant antigens with adjuvants. While composition of adjuvants is integral in defining the overall performance of an adjuvant, some physical parameters such as particle size, surface charge and surface modification may also contribute to the potency. In this review, we will try to highlight the role of particle size in controlling the immune responses to adjuvanted vaccines, with a focus on insoluble aluminum salts, oil-in-water emulsions, polymeric particles and liposomes.

Adjuvant Radioactive iodine 131 ablation in papillary microcarcinoma of thyroid: Saudi Arabian experience [corrected].

PubMed

Al-Qahtani, Khalid Hussain; Al Asiri, Mushabbab; Tunio, Mutahir A; Aljohani, Naji J; Bayoumi, Yasser; Fatani, Hanadi; AlHadab, Abdulrehman

2015-12-01

Papillary Microcarcinoma (PMC) of thyroid is a rare type of differentiated thyroid cancer (DTC), which according to the World Health Organization measures 1.0 cm or less. The gold standard of treatment of PMC is still controversy. Our aim was to contribute in resolving the debate on the therapeutic choices of the surgical and adjuvant I-131 (RAI) treatment in PMC. From 2000 to 2012, 326 patients were found to have PMC and were retrospectively reviewed for clinicopathological characteristics, treatment outcomes and prognostic factors. Mean age of cohort was 42.6 years (range: 18-76) and the mean tumor size was 0.61 cm ± 0.24; lymph node involvement was seen in 12.9 % of cases. Median follow up period was 8.05 years (1.62-11.4). Total 23 all site recurrences (7.13 %) were observed; more observed in patients without I-131 ablation (p <0.0001). Ten year DFS rates were 89.6 %. Cox regression Model analysis revealed size, histopathologic variants, multifocality, extrathyroidal extension, lymphovascular space invasion, nodal status, and adjuvant RAI ablation the important prognostic factors affecting DFS. Despite excellent DFS rates, a small proportion of patients with PMC develop recurrences after treatment. Adjuvant RAI therapy improves DFS in PMC patients with aggressive histopathologic variants, multifocality, ETE, LVSI, tumor size (> 0.5 cm) and lymph node involvement. Failure of RAI ablation to decrease risk in N1a/b supports prophylactic central neck dissection during thyroidectomy, however more trials are warranted. Adjuvant I-131 ablation following thyroidectomy in PMC patients, particularly with poor prognostic factors improves DFS rates.

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy.

PubMed

Findlay, John M; Castro-Giner, Francesc; Makino, Seiko; Rayner, Emily; Kartsonaki, Christiana; Cross, William; Kovac, Michal; Ulahannan, Danny; Palles, Claire; Gillies, Richard S; MacGregor, Thomas P; Church, David; Maynard, Nicholas D; Buffa, Francesca; Cazier, Jean-Baptiste; Graham, Trevor A; Wang, Lai-Mun; Sharma, Ricky A; Middleton, Mark; Tomlinson, Ian

2016-04-05

How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful.

New generation adjuvants--from empiricism to rational design.

PubMed

O'Hagan, Derek T; Fox, Christopher B

2015-06-08

Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vaccine adjuvant technology: from mechanistic concepts to practical applications.

PubMed

Degen, Winfried G J; Jansen, Theo; Schijns, Virgil E J C

2003-04-01

Distinct types of immune responses are required for efficient elimination of different pathogens. Programming of the desired type of immune response by safe nonreplicating vaccines requires suitable vaccine adjuvants. Adjuvants largely determine the magnitude and quality of immune responses specific for the coadministered antigen. Unfortunately, rational vaccine design requiring a rational choice of vaccine adjuvant, is hampered by a lack of knowledge about the mechanism(s) of vaccine adjuvant activity. The current review addresses different critical immunological processes possibly explaining adjuvant functions. In addition, we discuss traditional vaccine adjuvant formulations and their possible mode of action. Finally, we reflect on the latest technologies for the identification of novel adjuvants using molecular analysis of immune activation and functional genomics.

Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma.

PubMed

Marulli, Giuseppe; Faccioli, Eleonora; Bellini, Alice; Mammana, Marco; Rea, Federico

2017-08-01

Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.

Synthesis of Lymph Node-Targeting Adjuvants.

PubMed

Hanson, Melissa C; Irvine, Darrell J

2017-01-01

Molecular adjuvants based off of pattern recognition receptor agonists are capable of potently stimulating innate immunity and inducing protective immune responses to subunit antigens. One significant disadvantage to these small molecule adjuvants is their pharmacokinetic profile of entering the blood stream rather than the lymphatics after parental injection. In order to target molecular adjuvants to lymph nodes, we have developed nanoparticle carriers whose size has been optimized to avoid the blood and efficiently drain to lymph nodes (Hanson et al. Vaccine 33:861-8,2015; Hanson et al. J Clin Invest 125:2532-2546, 2015). This chapter describes in detail the materials and procedures necessary to synthesize liposome nanoparticle carriers of either hydrophobic or hydrophilic adjuvants, including synthesis tips, alternative equipment options, and pitfalls to avoid.

Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant

PubMed Central

Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita

2014-01-01

Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. PMID:24554695

Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

PubMed

Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Merkel, Tod J

2014-04-01

Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

Role of Adjuvant Chemoradiotherapy for Ampulla of Vater Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Kyubo; Chie, Eui Kyu; Jang, Jin-Young

2009-10-01

Purpose: To evaluate the role of adjuvant chemoradiotherapy for ampulla of Vater cancer. Methods and Materials: Between January 1991 and December 2002, 118 patients with ampulla of Vater cancer underwent en bloc resection. Forty-one patients received adjuvant chemoradiotherapy [RT(+) group], and 77 did not [RT(-) group]. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes, for a total dose of up to 40 Gy delivered in 2-Gy fractions, with a planned 2-week rest period halfway through the treatment period. Intravenous 5-fluorouracil (500 mg/m{sup 2}/day) was given on Days 1 to 3 of each split course. The medianmore » follow-up was 65 months. Results: The 5-year overall survival rate in the RT(-) and RT(+) groups was 66.9% and 52.8%, respectively (p = 0.2225). The 5-year locoregional relapse-free survival rate in the RT(-) and RT(+) groups was 79.9% and 80.2%, respectively (p = 0.9582). When age, type of operation, T stage, N stage, histologic differentiation, and the use of adjuvant chemoradiotherapy were incorporated into the Cox proportional hazard model, there was an improvement in the locoregional relapse-free survival rate (p = 0.0050) and a trend toward a longer overall survival (p = 0.0762) associated with the use of adjuvant chemoradiotherapy. Improved overall survival (p = 0.0235) and locoregional relapse-free survival (p = 0.0095) were also evident in patients with nodal metastasis. In contrast, enhanced locoregional control (p = 0.0319) did not result in longer survival in patients with locally advanced disease (p = 0.4544). Conclusions: Adjuvant chemoradiotherapy may enhance locoregional control and overall survival in patients with ampulla of Vater cancer after curative resection, especially in those with nodal involvement.« less

Manufacturing Methods for Liposome Adjuvants.

PubMed

Perrie, Yvonne; Kastner, Elisabeth; Khadke, Swapnil; Roces, Carla B; Stone, Peter

2017-01-01

A wide range of studies have shown that liposomes can act as suitable adjuvants for a range of vaccine antigens. Properties such as their amphiphilic character and biphasic nature allow them to incorporate antigens within the lipid bilayer, on the surface, or encapsulated within the inner core. However, appropriate methods for the manufacture of liposomes are limited and this has resulted in issues with cost, supply, and wider scale application of these systems. Within this chapter we explore manufacturing processes that can be used for the production of liposomal adjuvants, and we outline new manufacturing methods can that offer fast, scalable, and cost-effective production of liposomal adjuvants.

Antihyperalgesic and antiallodynic effect of sirolimus in rat model of adjuvant arthritis.

PubMed

Orhan, Cahide Elif; Önal, Aytül; Uyanıkgil, Yiğit; Ülker, Sibel

2013-04-05

Sirolimus is an immunosupressive drug that specifically inhibit the activation of T-lymphocytes. This study was undertaken to investigate whether treatment with sirolimus exert analgesic effect in rat adjuvant-induced arthritis, an animal model of rheumatoid arthritis. Arthritis was induced by a single subcutaneous injection of Freund's complete adjuvant to male Wistar rats that were divided into four groups; control (saline), vehicle (ethanol), sirolimus 0.75 and sirolimus 1.5. Sirolimus (0.75 and 1.5mg/kg/day) was administered intraperitoneally using Monday-Wednesday-Friday dosing schedule for 29 days, this dosing regimen revealed acceptable trough blood concentrations in arthritic rats. Adjuvant inoculation resulted in paw inflammation, hyperalgesia and allodynia as assessed by pletismometer, analgesymeter and dynamic plantar aesthesiometer respectively. Light microscopic evaluation of the arthritic metacarpophalangeal joints revealed synovial hypertrophy with inflammatory cellular infiltration, cartilage destruction and partial subchondral bone resorption. ELISA tests of serum TNF-α, IL-1β or IL-6 did not show any change in arthritic rats, while Western blotting analysis revealed a significant increase in TNF-α (P<0.001), but not IL-1β or IL-6, protein expression in the lumbar spinal cord of arthritic rats. Treatment with sirolimus significantly decreased the arthritic lesions (P<0.001) and paw swelling (P<0.05), alleviated the histological features in the metacarpophalangeal joint, resulted in antihyperalgesic and antiallodynic effects without affecting the locomotor activity and prevented the increased spinal cord TNF-α level (P<0.05). It seems that prevention of the increased TNF-α expression in the spinal cord may partially contribute to the antihyperalgesic effect of sirolimus in adjuvant arthritic rats and sirolimus could be a promising immunosupressive agent in the treatment of arthritic pain. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimal Use of Combined Modality Therapy in the Treatment of Esophageal Cancer.

PubMed

Shaikh, Talha; Meyer, Joshua E; Horwitz, Eric M

2017-07-01

Esophageal cancer is associated with a poor prognosis with 5-year survival rates of approximately 15% to 20%. Although patients with early stage disease may adequately be treated with a single modality, combined therapy typically consisting of neoadjuvant chemoradiation followed by esophagectomy is being adopted increasingly in patients with locally advanced disease. In patients who are not surgical candidates, definitive chemoradiation is the preferred treatment approach. All patients with newly diagnosed esophageal cancer should be evaluated in the multidisciplinary setting by a surgeon, radiation oncologist, and medical oncologist owing to the importance of each specialty in the management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural practice effect during cross-modal selective attention: Supra-modal and modality-specific effects.

PubMed

Xia, Jing; Zhang, Wei; Jiang, Yizhou; Li, You; Chen, Qi

2018-05-16

Practice and experiences gradually shape the central nervous system, from the synaptic level to large-scale neural networks. In natural multisensory environment, even when inundated by streams of information from multiple sensory modalities, our brain does not give equal weight to different modalities. Rather, visual information more frequently receives preferential processing and eventually dominates consciousness and behavior, i.e., visual dominance. It remains unknown, however, the supra-modal and modality-specific practice effect during cross-modal selective attention, and moreover whether the practice effect shows similar modality preferences as the visual dominance effect in the multisensory environment. To answer the above two questions, we adopted a cross-modal selective attention paradigm in conjunction with the hybrid fMRI design. Behaviorally, visual performance significantly improved while auditory performance remained constant with practice, indicating that visual attention more flexibly adapted behavior with practice than auditory attention. At the neural level, the practice effect was associated with decreasing neural activity in the frontoparietal executive network and increasing activity in the default mode network, which occurred independently of the modality attended, i.e., the supra-modal mechanisms. On the other hand, functional decoupling between the auditory and the visual system was observed with the progress of practice, which varied as a function of the modality attended. The auditory system was functionally decoupled with both the dorsal and ventral visual stream during auditory attention while was decoupled only with the ventral visual stream during visual attention. To efficiently suppress the irrelevant visual information with practice, auditory attention needs to additionally decouple the auditory system from the dorsal visual stream. The modality-specific mechanisms, together with the behavioral effect, thus support the visual

Personalized treatment of women with early breast cancer: a risk-group specific cost-effectiveness analysis of adjuvant chemotherapy accounting for companion prognostic tests OncotypeDX and Adjuvant!Online.

PubMed

Jahn, Beate; Rochau, Ursula; Kurzthaler, Christina; Hubalek, Michael; Miksad, Rebecca; Sroczynski, Gaby; Paulden, Mike; Bundo, Marvin; Stenehjem, David; Brixner, Diana; Krahn, Murray; Siebert, Uwe

2017-10-16

Due to high survival rates and the relatively small benefit of adjuvant therapy, the application of personalized medicine (PM) through risk stratification is particularly beneficial in early breast cancer (BC) to avoid unnecessary harms from treatment. The new 21-gene assay (OncotypeDX, ODX) is a promising prognostic score for risk stratification that can be applied in conjunction with Adjuvant!Online (AO) to guide personalized chemotherapy decisions for early BC patients. Our goal was to evaluate risk-group specific cost effectiveness of adjuvant chemotherapy for women with early stage BC in Austria based on AO and ODX risk stratification. A previously validated discrete event simulation model was applied to a hypothetical cohort of 50-year-old women over a lifetime horizon. We simulated twelve risk groups derived from the joint application of ODX and AO and included respective additional costs. The primary outcomes of interest were life-years gained, quality-adjusted life-years (QALYs), costs and incremental cost-effectiveness (ICER). The robustness of results and decisions derived were tested in sensitivity analyses. A cross-country comparison of results was performed. Chemotherapy is dominated (i.e., less effective and more costly) for patients with 1) low ODX risk independent of AO classification; and 2) low AO risk and intermediate ODX risk. For patients with an intermediate or high AO risk and an intermediate or high ODX risk, the ICER is below 15,000 EUR/QALY (potentially cost effective depending on the willingness-to-pay). Applying the AO risk classification alone would miss risk groups where chemotherapy is dominated and thus should not be considered. These results are sensitive to changes in the probabilities of distant recurrence but not to changes in the costs of chemotherapy or the ODX test. Based on our modeling study, chemotherapy is effective and cost effective for Austrian patients with an intermediate or high AO risk and an intermediate or high

Adoption of endovenous laser treatment as the primary treatment modality for varicose veins: the Auckland City Hospital experience.

PubMed

Fernando, Ruchira S W; Muthu, Carl

2014-08-01

To assess the effectiveness of adopting endovenous laser treatment (EVLT) as the primary treatment modality for varicose veins at Auckland City Hospital (Auckland, New Zealand). The outcomes of 354 consecutive EVLT procedures performed between 2007 and 2013 were reviewed. Data was collected from a prospectively maintained procedural database and by retrospective chart review. Of the 319 patients who had an ultrasound, at 1 month post-procedure there was a saphenous vein occlusion rate of 96%. Side effects were minimal with no cases of DVT or skin burns and one case of self-limiting neuralgia. The procedure was well tolerated with a median pain score of 3. Since the adoption of EVLT there has been a large increase in the number of patients treated for varicose veins (28 in 2007 compared to 176 in 2013). EVLT is a safe and effective treatment for varicose veins and its adoption has allowed a large increase in the number of varicose vein patients treated at Auckland City Hospital.

Initial Experience With Low-Dose Methotrexate as an Adjuvant Treatment for Rapidly Recurrent Nonvasculitic Laryngotracheal Stenosis.

PubMed

Rosow, David E; Ahmed, Jamal

2017-02-01

Adult laryngotracheal stenosis (LTS) is typically managed surgically, but some patients fail treatment because of rapid restenosis or granulation tissue formation. The need for frequent surgery or tracheostomy reduces the quality of life in these patients and poses a significant challenge for the treating physician. New adjuvant treatments are required to reduce the surgical burden of this condition. To examine whether patients with rapidly recurrent nonvasculitic LTS who fail surgical management of their stenosis (ie, requiring dilation more frequently than every 6 months) experience longer intervals between surgical procedures when receiving adjuvant treatment with low-dose methotrexate. This study was a retrospective case series study of patients treated with methotrexate from January 2014 to January 2016 at a tertiary academic medical center. Participants were 10 patients with LTS without any diagnosis of vasculitis or granulomatous disease who underwent low-dose methotrexate therapy. Once-weekly treatment with oral methotrexate, 15 or 20 mg. The mean number of days between operations before and after starting methotrexate therapy was compared. Clinical courses and adverse effects of each patient were also reviewed. Among 10 patients, the mean (SD) age at the outset of study inclusion was 52 (19) years; 8 were female and 2 were male. All 10 patients experienced some clinical improvement. Three patients who were previously tracheostomy dependent were able to be decannulated. Two other patients who were tracheostomy dependent and had failed endoscopic management of their granulation tissue had complete resolution. In 6 patients who underwent at least 1 surgical procedure before and after the initiation of methotrexate treatment, the mean (SD) interval between operations increased from 61 (35) days (95% CI, 26-96 days) before starting methotrexate therapy to 312 (137) days (95% CI, 175-449 days) after starting methotrexate therapy, for an absolute difference of

Outcomes of curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma of long bone.

PubMed

Kim, Wanlim; Han, Ilkyu; Kim, Eo Jin; Kang, Seungcheol; Kim, Han-Soo

2015-06-01

Low-grade chondrosarcoma of long bones can be treated successfully with extended intralesional curettage using adjuvants. However, there is no study reporting the use of anhydrous alcohol as an adjuvant in the treatment of low-grade chondrosarcoma. We asked (1) whether intralesional curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma is associated with good oncologic outcomes; and we report (2) the complications of the procedure. Thirty-six patients (13 men, 23 women) with a mean age of 46 years (range, 18-67 years) were treated for low-grade chondrosarcoma and followed up for a median of 62 months (range, 24-169 months). After intralesional curettage, and additional burring, anhydrous alcohol was used as an adjuvant therapy. At the time of last follow-up, there were no local recurrences or distant metastases. Six patients developed complications: 4 postoperative fractures (11%), 1 intra-articular loose body (3%) and 1 postoperative joint stiffness (3%). Anhydrous alcohol is a reasonable adjuvant for the curettage of low-grade chondrosarcoma of long bones. A long-term follow-up study is necessary, considering the slow biological progression of low-grade chondrosarcoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sequential versus "sandwich" sequencing of adjuvant chemoradiation for the treatment of stage III uterine endometrioid adenocarcinoma.

PubMed

Lu, Sharon M; Chang-Halpenny, Christine; Hwang-Graziano, Julie

2015-04-01

To compare the efficacy and tolerance of adjuvant chemotherapy and radiotherapy delivered in sequential (chemotherapy followed by radiation) versus "sandwich" fashion (chemotherapy, interval radiation, and remaining chemotherapy) after surgery in patients with FIGO stage III uterine endometrioid adenocarcinoma. From 2004 to 2011, we identified 51 patients treated at our institution fitting the above criteria. All patients received surgical staging followed by adjuvant chemoradiation (external-beam radiation therapy (EBRT) with or without high-dose rate (HDR) vaginal brachytherapy (VB)). Of these, 73% and 27% of patients received their adjuvant therapy in sequential and sandwich fashion, respectively. There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Thirty-nine (76%) patients had stage IIIC disease. The majority of patients received 6 cycles of paclitaxel with carboplatin or cisplatin. Median EBRT dose was 45 Gy and 54% of patients received HDR VB boost (median dose 21 Gy). There were no significant differences in the estimated 5-year overall survival, local progression-free survival, and distant metastasis-free survival between the sequential and sandwich groups: 87% vs. 77% (p=0.37), 89% vs. 100% (p=0.21), and 78% vs. 85% (p=0.79), respectively. No grade 3-4 genitourinary or gastrointestinal toxicities were reported in either group. There was a trend towards higher incidence of grade 3-4 hematologic toxicity in the sandwich group. Adjuvant chemoradiation for FIGO stage III endometrioid uterine cancer given in either sequential or sandwich fashion appears to offer equally excellent early clinical outcomes and acceptably low toxicity. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of adjuvant radiotherapy for localized extrahepatic bile duct cancer

PubMed Central

Kim, Yi-Jun; Min, Seog Ki; Nam, Eun Mi

2017-01-01

Objective: To evaluate the benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic bile duct (EHBD) cancer. Methods: From 1997 to 2015, 59 patients with EHBD cancer were the subject of this study; 36 patients not undergoing adjuvant treatment after surgery (observation group) and 23 patients receiving adjuvant RT (RT group) were compared. Microscopic residual disease (R1) was in 9 (25%) patients and 5 (22%) patients, and macroscopic residual disease (R2) was in 2 (6%) patients and 6 (26%) patients in the observation and RT groups, respectively. Adjuvant RT was delivered to the tumour bed and regional lymph nodes up to 50.4 Gy (range, 45–61 Gy). Results: With a median follow-up of 19 months, local recurrence was observed in 10 (28%) patients and 2 (9%) patients in the observation and RT groups, respectively. On univariate analysis, the 5-year local recurrence-free survival (LRFS) rates were 50% in the observation group and 54% in the RT group (p = 0.401). The 5-year overall survival (OS) rates were 29.3% in the observation group and 26.3% in the RT group (p = 0.602). On multivariable analysis, however, adjuvant RT significantly improved LRFS [hazard ratio (HR), 0.310; 95% confidence interval (CI), 0.100–0.963; p = 0.043] and had a trend towards increased OS (HR, 0.491; 95% CI, 0.219–1.102; p = 0.085). Resection margin (RM) status was also correlated with LRFS (HR for R1 6.134, 95% CI 2.051–18.344; and HR for R2 18.551, 95% CI 3.680–93.520; p < 0.001) and OS (HR for R1 1.816, 95% CI 0.853–3.867; and HR for R2 3.564, 95% CI 1.175–10.809; p = 0.054). Conclusion: RM status was a significant prognosticator of EHBD cancer, and adjuvant RT improved local control rate; thereby, survival rate might be increased. Advances in knowledge: The benefit of adjuvant RT in EHBD cancer was demonstrated via comparison with observation group. PMID:28118028

Adjuvant Treatment with Yupingfeng Formula for Recurrent Respiratory Tract Infections in Children: A Meta-analysis of Randomized Controlled Trials.

PubMed

Song, Tao; Hou, Xiaoli; Yu, Xiaohui; Wang, Zhen; Wang, Ruiren; Li, Yanling; Hu, Dan; Wang, Xiaohong; Xiao, Zhengzheng; Sui, Yong; Zhu, Chunhong; Wang, Jing

2016-07-01

This meta-analysis aimed to evaluate the immunomodulating function of Yupingfeng Formula (YPFF) in children with recurrent respiratory tract infections (RRTIs). The PubMed, EMBASE, Cochrane Library, CNKI and WanFang databases were searched for randomized controlled trials comparing with and without YPFF for RRTIs in children. Twelve trials with 1236 patients were identified. Adjuvant treatment with YPFF significantly increased serum levels of IgA (weighted mean difference [WMD] 0.33 mg/mL; 95% confidence interval [CI] 0.20 to 0.45), IgG (WMD 1.36 mg/mL; 95% CI 1.06 to 1.65), IgM (WMD 0.16 mg/mL; 95% CI 0.02 to 0.31), and CD3(+) T-lymphocytes (WMD 10.16%; 95% CI 4.62 to 15.69) but not CD4(+) T-lymphocytes (WMD 3.16%; 95% CI -0.27 to 6.59) and CD8(+) T-lymphocytes (WMD -0.84%; 95% CI -2.50 to 0.81). YPFF also reduced the frequency of RRTIs (WMD -3.80 times; 95% CI -4.86 to -2.74) and increased total effective rates of symptom improvement (risk ratio: 1.44; 95% CI 1.19 to 1.75). Adjuvant treatment with YPFF could improve total clinical effective rate and decrease the frequency of respiratory tract infections in children with RRTIs. The beneficial effects of YPFF may be correlated to its immunomodulating action. More well-designed trials with larger sample sizes are needed to evaluate its efficacy and safety. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Bilateral Salpingo-Oophorectomy Versus GnRH Analogue in the Adjuvant Treatment of Premenopausal Breast Cancer Patients: Cost-Effectiveness Evaluation of Breast Cancer Outcome, Ovarian Cancer Prevention and Treatment.

PubMed

Ferrandina, Gabriella; Amadio, Giulia; Marcellusi, Andrea; Azzolini, Elena; Puggina, Anna; Pastorino, Roberta; Ricciardi, Walter; Scambia, Giovanni

2017-11-01

BACKGROUND AND OBJECTIVE: There is no available evidence to recommend gonadotropin-releasing hormone (GnRH) analogue-based ovarian suppression versus bilateral salpingo-oophorectomy (BSO) in the adjuvant treatment of early breast cancer, since the two approaches are considered equivalent in terms of oncologic outcome. The role of surgical ovarian ablation has been revitalized based on the advances of minimally invasive surgery, and a better understanding of clinical and molecular basis of hereditary breast/ovarian cancer syndromes. The aim of this study is to analyze the cost-effectiveness of laparoscopic BSO and GnRH analogue administration in patients aged 40-49 years with hormone-sensitive breast cancer. A probabilistic decision tree model was developed to evaluate costs and outcomes of ovarian ablation through laparoscopic BSO, or ovarian suppression through monthly injections of GnRH analogue. Results were expressed as incremental costs per quality-adjusted life years (QALYs) gained. Laparoscopic BSO strategy was associated with a lower mean total cost per patient than GnRH treatment, and considering the difference in terms of QALYs, the incremental effectiveness did not demonstrate a notable difference between the two approaches. From the National Health Service perspective, and for a time horizon of 5 years, laparoscopic BSO was the dominant option compared to GnRH treatment; laparoscopic BSO was less expensive than GnRH, €2385 [95% confidence interval (CI) = 2044, 2753] vs €7093 (95% CI = 3409, 12,105), respectively, and more effective. Surgical ovarian ablation is more cost-effective than GnRH administration in the adjuvant treatment of hormone-sensitive breast cancer patients aged 40-49 years, and the advantage of preventing ovarian cancer through laparoscopic BSO should be considered.

A comparison of oncological outcomes between transoral surgical and non-surgical treatment protocols in the management of oropharyngeal squamous cell carcinoma.

PubMed

Kao, S S; Micklem, J; Ofo, E; Edwards, S; Dhatrak, D; Foreman, A; Krishnan, S; Hodge, J-C

2018-04-01

The incidence of oropharyngeal squamous cell carcinoma in the Western world is increasing, with the human papillomavirus epidemic implicated in this observed trend. The optimal treatment modality is yet undetermined regarding oncological outcomes. This study comprised 98 patients with oropharyngeal squamous cell carcinoma, treated with either primary transoral surgery with adjuvant therapy or primary chemoradiotherapy with curative intent, between 2008 and 2012. Clinicopathological characteristics including tumour-node-metastasis stage, human papillomavirus status, treatment modality, recurrence and overall survival were collated. Five per cent of primary surgical patients had locoregional recurrences compared with 25 per cent of primary chemoradiotherapy patients. A lower rate of locoregional recurrence was observed in the human papillomavirus positive group. This paper reports higher rates of overall survival and local control for oropharyngeal squamous cell carcinoma treated with primary surgery compared with primary chemoradiotherapy. This reflects overall lower tumour stage and higher human papillomavirus status in this group.

Treatment Needs of Driving While Intoxicated Offenders: The Need for a Multi-modal Approach to Treatment

PubMed Central

Mullen, Jillian; Ryan, Stacy R.; Mathias, Charles W.; Dougherty, Donald M.

2015-01-01

Objective This study aimed to characterize and compare the treatment needs of adults with driving while intoxicated (DWI) offenses recruited from a correctional residential treatment facility and the community to provide recommendations for treatment development. Method A total of 119 adults (59 Residential, 60 Community) with at least one DWI offense were administered clinical diagnostic interviews to assess substance use disorders and completed a battery of questionnaires assessing demographic characteristics, legal history, psychiatric diagnoses, medical diagnoses, and health care utilization. Results Almost all (96.6%) DWI offenders met clinical diagnostic criteria for an alcohol use disorder, approximately half of the sample also met diagnostic criteria for co-morbid substance use disorders and a substantial proportion also reported psychiatric and medical co-morbidities. However, a high percentage were not receiving treatment for these issues, most likely as a result of having limited access to care as the majority of participants had no current health insurance (64.45%) or primary care physician (74.0%). The residential sample had more extensive criminal histories compared to the community sample but was generally representative of the community in terms of their clinical characteristics. For instance, the groups did not differ in rates of substance use, psychiatric and medical health diagnoses or in the treatment of such issues, with the exception of alcohol abuse treatment. Conclusions DWI offenders represent a clinical population with high levels of complex and competing treatment needs which are not currently being met. Our findings demonstrate the need for standardized screening of DWI offenders and call for the development of a multi-modal treatment approach in efforts to reduce recidivism. PMID:25664371

Herbal Medicine and Acupuncture for Breast Cancer Palliative Care and Adjuvant Therapy

PubMed Central

Liao, Guo-Shiou; Shyur, Lie-Fen

2013-01-01

Breast cancer is a life-threatening disease among women worldwide with annual rates of reported incidence and death increasing alarmingly. Chemotherapy is a recommended and effective treatment option for breast cancer; however, the narrow therapeutic indices and varied side effects of currently approved drugs present major hurdles in increasing its effectiveness. An increasing number of literature evidence indicate that complementary and alternative medicine (CAM) used in treatment-related symptom control and alleviation of side effects plays an important role in increasing survival rate and quality of life in breast cancer patients. This review focuses on the use of herbal medicines and acupuncture in palliative care and as adjuvants in the treatment of breast cancer. Herbal medicinal treatments, the correlation of clinical use with demonstrated in vitro and in vivo mechanisms of action, and the use of certain acupoints in acupuncture are summarized. The aim of this review is to facilitate an understanding of the current practice and usefulness of herbal medicine and acupuncture as adjuvants in breast cancer therapy. PMID:23840256

Effect of Antioxidant Vitamins as Adjuvant Therapy for Sudden Sensorineural Hearing Loss: Systematic Review Study.

PubMed

Ibrahim, Iman; Zeitouni, Anthony; da Silva, Sabrina Daniela

2018-06-22

Sudden sensorineural hearing loss (SSNHL) is an otological emergency of unknown etiology. Recent reports showed that antioxidant drugs can benefit patients with SSNHL. This study attempted to evaluate the effect of adding antioxidant vitamins as an adjuvant therapy alongside with corticosteroids. To evaluate the effects of the 3 major antioxidant vitamins (A, C, and E) as an adjuvant therapy, administered with corticosteroids, for the treatment of SSNHL in adult patients (≥18 years). MEDLINE, EMBASE, PubMed, Web of Science and Cochrane electronic databases from January 1, 1995, through September 25, 2017. Published studies of adult patients who received antioxidant vitamins (A, C, E, or any combination of these vitamins) as an adjuvant therapy in addition to the regular treatment (corticosteroids) for SSNHL. Quality assessment was performed using the Cochrane Collaboration Tool for Assessing Risk of Bias. Each study had a control group (conventional treatment + placebo) and a trial group (antioxidant vitamin(s) + conventional treatment). From 446 manuscripts identified in the literature, 3 studies were included in the review with 279 patients. The most common vitamins used to treat SSNHL were the 3 major antioxidant vitamins A, C, and E, combined sometimes with other antioxidants such as selenium. The success of the treatment is increased in patients who received antioxidant vitamins in combination with conventional therapy. © 2018 S. Karger AG, Basel.

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new.

PubMed

Boyle, John; Czito, Brian; Willett, Christopher; Palta, Manisha

2015-08-01

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates.

Adjuvant radiation therapy for pancreatic cancer: a review of the old and the new

PubMed Central

Boyle, John; Czito, Brian; Willett, Christopher

2015-01-01

Surgery represents the only potential curative treatment option for patients diagnosed with pancreatic adenocarcinoma. Despite aggressive surgical management for patients deemed to be resectable, rates of local recurrence and/or distant metastases remain high, resulting in poor long-term outcomes. In an effort to reduce recurrence rates and improve survival for patients having undergone resection, adjuvant therapies (ATs) including chemotherapy and chemoradiation therapy (CRT) have been explored. While adjuvant chemotherapy has been shown to consistently improve outcomes, the data regarding adjuvant radiation therapy (RT) is mixed. Although the ability of radiation to improve local control has been demonstrated, it has not always led to improved survival outcomes for patients. Early trials are flawed in their utilization of sub-optimal radiation techniques, limiting their generalizability. Recent and ongoing trials incorporate more optimized RT approaches and seek to clarify its role in treatment strategies. At the same time novel radiation techniques such as intensity modulated RT (IMRT) and stereotactic body RT (SBRT) are under active investigation. It is hoped that these efforts will lead to improved disease-related outcomes while reducing toxicity rates. PMID:26261730

Advances in aluminum hydroxide-based adjuvant research and its mechanism.

PubMed

He, Peng; Zou, Yening; Hu, Zhongyu

2015-01-01

In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants.

Advances in aluminum hydroxide-based adjuvant research and its mechanism

PubMed Central

He, Peng; Zou, Yening; Hu, Zhongyu

2015-01-01

In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants. PMID:25692535

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed

Korbelik, M; Naraparaju, V R; Yamamoto, N

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed Central

Korbelik, M.; Naraparaju, V. R.; Yamamoto, N.

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours. PMID:9010027

Risk of endocrine pancreatic insufficiency in patients receiving adjuvant chemoradiation for resected gastric cancer.

PubMed

Gemici, Cengiz; Sargin, Mehmet; Uygur-Bayramicli, Oya; Mayadagli, Alpaslan; Yaprak, Gokhan; Dabak, Resat; Kocak, Mihriban

2013-05-01

Adjuvant radiotherapy combined with 5-fluorouracil based chemotherapy has become the new standard after curative resection in high risk gastric cancer. Beside many complications due to surgery, the addition of chemotherapy and radiotherapy as adjuvant treatment may lead to both acute and late toxicities. Pancreatic tissue irradiation during this adjuvant treatment because of incidental and unavoidable inclusion of the organ within the radiation field may affect exocrine and endocrine functions of the organ. Fifty-three patients with gastric adenocarcinoma were evaluated for adjuvant chemoradiotherapy after surgery. While 37 out of 53 patients were treated postoperatively due to either serosal or adjacent organ or lymph node involvement, 16 patients without these risk factors were followed up regularly without any additional treatment and they served as the control group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1c), insulin and C-peptide levels were measured in the control and study groups after the surgery and 6 months and 1 year later. At the baseline there was no difference in FBG, HbA1c, C-peptide and insulin levels between the control and the study groups. At the end of the study there was a statistically significant decline in insulin and C-peptide levels in the study group, (7.5 ± 6.0 vs 4.5 ± 4.4 IU/L, p: 0.002 and 2.3 ± 0.9 vs 1.56 ± 0.9 ng/ml, p: 0.001) respectively. Adjuvant radiotherapy in gastric cancer leads to a decrease in beta cell function and insulin secretion capacity of the pancreas with possible diabetes risk. Radiation-induced pancreatic injury and late effects of radiation on normal pancreatic tissue are unknown, but pancreas is more sensitive to radiation than known. This organ should be studied extensively in order to determine the tolerance doses and it should be contoured during abdominal radiotherapy planning as an organ at risk. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Cost-effectiveness of the 21-gene assay for guiding adjuvant chemotherapy decisions in early breast cancer.

PubMed

Paulden, Mike; Franek, Jacob; Pham, Ba'; Bedard, Philippe L; Trudeau, Maureen; Krahn, Murray

2013-01-01

Adjuvant chemotherapy decisions in early breast cancer are complex. The 21-gene assay can potentially aid such decisions, but costs US $4175 per patient. Adjuvant! Online is a freely available decision aid. We evaluate the cost-effectiveness of using the 21-gene assay in conjunction with Adjuvant! Online, and of providing adjuvant chemotherapy conditional upon risk classification. A probabilistic Markov decision model simulated risk classification, treatment, and the natural history of breast cancer in a hypothetical cohort of 50-year-old women with lymph node-negative, estrogen receptor- and/or progesterone receptor-positive, human epidermal growth factor receptor 2/neu-negative early breast cancer. Cost-effectiveness was considered from an Ontario public-payer perspective by deriving the lifetime incremental cost (2012 Canadian dollars) per quality-adjusted life-year (QALY) for each strategy, and the probability each strategy is cost-effective, assuming a willingness-to-pay of $50,000 per QALY. The 21-gene assay has an incremental cost per QALY in patients at low, intermediate, or high Adjuvant Online! risk of $22,440 (probability cost-effective 78.46%), $2,526 (99.40%), or $1,111 (99.82%), respectively. In patients at low (high) 21-gene assay risk, adjuvant chemotherapy increases (reduces) costs and worsens (improves) health outcomes. For patients at intermediate 21-gene assay risk and low, intermediate, or high Adjuvant! Online risk, chemotherapy has an incremental cost per QALY of $44,088 (50.59%), $1,776 (77.65%), or $1,778 (82.31%), respectively. The 21-gene assay appears cost-effective, regardless of Adjuvant! Online risk. Adjuvant chemotherapy appears cost-effective for patients at intermediate or high 21-gene assay risk, although this finding is uncertain in patients at intermediate 21-gene assay and low Adjuvant! Online risk. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights

Lack of Prognostic Impact of Adjuvant Radiation on Oncologic Outcomes in Elderly Women with Breast Cancer.

PubMed

Omidvari, Shapour; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Moaddabshoar, Leila; Dayani, Maliheh; Mosalaei, Ahmad; Ahmadloo, Niloofar; Ansari, Mansour; Mohammadianpanah, Mohammad

2015-01-01

Radiotherapy plays an important role as adjuvant treatment in locally advanced breast cancer and in those patients who have undergone breast-conserving surgery. This study aimed to investigate the prognostic impact of adjuvant radiation on oncologic outcomes in elderly women with breast cancer. In this retrospective study, we reviewed and analyzed the characteristics, treatment outcome and survival of elderly women (aged ≥ 60 years) with breast cancer who were treated and followed-up between 1993 and 2014. The median follow up for the surviving patients was 38 (range 3-207) months. One hundred and seventy-eight patients with a median age of 74 (range 60-95) years were enrolled in the study. Of the total, 60 patients received postoperative adjuvant radiation (radiation group) and the remaining 118 did not (control group). Patients in the radiation group were significantly younger than those in the control group (P value=0.004). In addition, patients in radiation group had higher node stage (P value<0.001) and disease stage (P=0.003) and tended to have higher tumor grade (P=0.031) and received more frequent (P value <0.001) adjuvant and neoadjuvant chemotherapy compared to those in the control group. There was no statistically significant difference between two groups regarding the local control, disease-free survival and overall survival rates. In this study, we did not find a prognostic impact for adjuvant radiation on oncologic outcomes in elderly women with breast cancer.

A phase III randomized trial comparing adjuvant concomitant chemoradiotherapy versus standard adjuvant chemotherapy followed by radiotherapy in operable node-positive breast cancer: Final results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rouesse, Jacques; Lande, Brigitte de la; Bertheault-Cvitkovic, Frederique

Purpose: To compare concomitant and sequential adjuvant chemoradiotherapy regimens in node-positive, operable breast cancer patients. Methods and Materials: This was a randomized, French, multicenter, phase III trial enrolling 638 eligible women with prior breast surgery and positive axillary dissection. Patients in Arm A received 500 mg/m{sup 2} 5-fluorouracil, 12 mg/m{sup 2} mitoxantrone, and 500 mg/m{sup 2} cyclophosphamide, with concomitant radiotherapy (50 Gy {+-} 10-20-Gy boost). Patients in Arm B received 500 mg/m{sup 2} 5-fluorouracil, 60 mg/m{sup 2} epirubicin, and 500 mg/m{sup 2} cyclophosphamide, with subsequent radiotherapy. Chemotherapy was administered on Day 1 every 21 days for 4 cycles. Results: Medianmore » treatment durations were 64 and 126 days (Arms A and B, respectively), with no significant difference in overall or disease-free survival. Five-year locoregional relapse-free survival favored patients with conservative surgery (two thirds of the population), with less local and/or regional recurrence in Arm A than in Arm B (3% vs. 9%; p 0.01). Multivariate analysis in this subgroup showed a 2.8-fold increased risk of locoregional recurrence with sequential chemoradiotherapy, independent of other prognostic factors (p = 0.027). Febrile neutropenia and Grade 3-4 leukopenia were significantly more frequent in Arm A. Subclinical left ventricular ejection fraction events at 1 year were more frequent with concomitant radiotherapy (p = 0.02). Conclusions: Concomitant radiotherapy with adjuvant fluorouracil, mitoxantrone, and cyclophosphamide has significantly better locoregional control in node-positive breast cancer after conservative surgery and 50% shorter treatment, albeit with slightly more acute toxicity. With mitoxantrone no longer available for adjuvant breast cancer treatment, alternative concomitant chemoradiotherapy studies are needed.« less

Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age

PubMed Central

Vesikari, Timo; Pepin, Stéphanie; Kusters, Inca; Hoffenbach, Agnès; Denis, Martine

2012-01-01

Vaccines were urgently needed in 2009 against A/H1N1 pandemic influenza. Based on the H5N1 experience, it was originally thought that 2 doses of an adjuvanted vaccine were needed for adequate immunogenicity. We tested H1N1 vaccines with or without AF03, a squalene-based adjuvant, in children. Two randomized, open-label, trials were conducted. Participants 3–17 y received two injections of 3.8 µg or 7.5 µg hemagglutinin (HA) with adjuvant or 15 µg HA without adjuvant. Participants aged 6–35 mo received two injections of 1.9 µg or 3.8 µg HA with full or half dose adjuvant or 7.5 µg HA without adjuvant. All subjects 3 to 17 y reached seroprotection (hemagglutination inhibition (HI) titer ≥ 40) after the first dose of the adjuvanted vaccine, and 94% and 98% in the 3–8 and 9–17 y groups respectively with the non-adjuvanted vaccine. In children aged 6–35 mo responses were modest after one dose, but after two doses virtually all children were seroprotected regardless of HA or adjuvant dose. In this age group, antibody titers were 5 to 7 times higher after adjuvanted than non-adjuvanted vaccine. The higher responses with the adjuvanted vaccine were also reflected as better antibody persistence. There was no clustering of adverse events that would be suggestive of a safety signal. While a single injection was sufficient in subjects from 3 y, in children aged 6–35 mo two injections of this A/H1N1 pandemic influenza vaccine were required. Formulation of this vaccine with adjuvant provided a significant advantage for immunogenicity in the latter age group. PMID:22906943

On modal cross-coupling in the asymptotic modal limit

NASA Astrophysics Data System (ADS)

Culver, Dean; Dowell, Earl

2018-03-01

The conditions under which significant modal cross-coupling occurs in dynamical systems responding to high-frequency, broadband forcing that excites many modes is studied. The modal overlap factor plays a key role in the analysis of these systems as the modal density (the ratio of number of modes to the frequency bandwidth) becomes large. The modal overlap factor is effectively the ratio of the width of a resonant peak (the damping ratio times the resonant frequency) to the average frequency interval between resonant peaks (or rather, the inverse of the modal density). It is shown that this parameter largely determines whether substantial modal cross-coupling occurs in a given system's response. Here, two prototypical systems are considered. The first is a simple rectangular plate whose significant modal cross-coupling is the exception rather than the norm. The second is a pair of rectangular plates attached at a point where significant modal cross-coupling is more likely to occur. We show that, for certain cases of modal density and damping, non-negligible cross coupling occurs in both systems. Under similar circumstances, the constraint force between the two plates in the latter system becomes broadband. The implications of this for using Asymptotic Modal Analysis (AMA) in multi-component systems are discussed.

Mental Health Disorder Therapeutic Modalities Modified for the GMS.

PubMed

Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

2017-12-01

Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. The finding of this review confirms the

Experiential Education, Outdoor Adventure As a Modality in Residential Treatment. A Survey of Programs, Principles, Research and Practice.

ERIC Educational Resources Information Center

Duindam, Ton

Orthopedagogisch Centrum (OC) Michiel is a multifunctional regional institution in the Netherlands that serves troubled families and youth at risk. Outdoor programs are used as a treatment modality for adolescents with behavior disorders, drug addictions, or criminal records. Outward Bound was the first experiential outdoor program in the…

Multi-Modality Imaging in the Evaluation and Treatment of Mitral Regurgitation.

PubMed

Bouchard, Marc-André; Côté-Laroche, Claudia; Beaudoin, Jonathan

2017-10-13

Mitral regurgitation (MR) is frequent and associated with increased mortality and morbidity when severe. It may be caused by intrinsic valvular disease (primary MR) or ventricular deformation (secondary MR). Imaging has a critical role to document the severity, mechanism, and impact of MR on heart function as selected patients with MR may benefit from surgery whereas other will not. In patients planned for a surgical intervention, imaging is also important to select candidates for mitral valve (MV) repair over replacement and to predict surgical success. Although standard transthoracic echocardiography is the first-line modality to evaluate MR, newer imaging modalities like three-dimensional (3D) transesophageal echocardiography, stress echocardiography, cardiac magnetic resonance (CMR), and computed tomography (CT) are emerging and complementary tools for MR assessment. While some of these modalities can provide insight into MR severity, others will help to determine its mechanism. Understanding the advantages and limitations of each imaging modality is important to appreciate their respective role for MR assessment and help to resolve eventual discrepancies between different diagnostic methods. With the increasing use of transcatheter mitral procedures (repair or replacement) for high-surgical-risk patients, multimodality imaging has now become even more important to determine eligibility, preinterventional planning, and periprocedural guidance.

Cost-utility analysis of adjuvant chemotherapy in patients with stage III colon cancer in Thailand.

PubMed

Lerdkiattikorn, Panattharin; Chaikledkaew, Usa; Lausoontornsiri, Wirote; Chindavijak, Somjin; Khuhaprema, Thirawud; Tantai, Narisa; Teerawattananon, Yot

2015-01-01

In Thailand, there has been no economic evaluation study of adjuvant chemotherapy for stage III colon cancer patients after resection. This study aims to evaluate the cost-utility of all chemotherapy regimens currently used in Thailand compared with the adjuvant 5-fluorouracil/leucovorin (5-FU/LV) plus capecitabine as the first-line therapy for metastatic disease in patients with stage III colon cancer after resection. A cost-utility analysis was performed to estimate the relevant lifetime costs and health outcomes of chemotherapy regimens based on a societal perspective using a Markov model. The results suggested that the adjuvant 5-FU/LV plus capecitabine as the first-line therapy for metastatic disease would be the most cost-effective chemotherapy. The adjuvant FOLFOX and FOLFIRI as the first-line treatment for metastatic disease would be cost-effective with an incremental cost-effectiveness ratio of 299,365 Thai baht per QALY gained based on a societal perspective if both prices of FOLFOX and FOLFIRI were decreased by 40%.

Opioid adjuvant strategy: improving opioid effectiveness.

PubMed

Bihel, Frédéric

2016-01-01

Opioid analgesics continue to be the mainstay of pharmacologic treatment of moderate to severe pain. Many patients, particularly those suffering from chronic pain, require chronic high-dose analgesic therapy. Achieving clinical efficacy and tolerability of such treatment regimens is hampered by the appearance of opioid-induced side effects such as tolerance, hyperalgesia and withdrawal syndrome. Among the therapeutic options to improve the opioid effectiveness, this current review focuses on strategies combining opioids to other drugs that can modulate opioid-mediated effects. We will discuss about experimental evidences reported for several potential opioid adjuvants, including N-methyl-D-aspartate receptor antagonists, 5-HT7 agonists, sigma-1 antagonists, I2-R ligands, cholecystokinin antagonists, neuropeptide FF-R antagonists and toll-like receptor 4 antagonists.

Quality of Life in 807 Patients with Vestibular Schwannoma: Comparing Treatment Modalities.

PubMed

Soulier, Géke; van Leeuwen, Bibian M; Putter, Hein; Jansen, Jeroen C; Malessy, Martijn J A; van Benthem, Peter Paul G; van der Mey, Andel G L; Stiggelbout, Anne M

2017-07-01

Objective In vestibular schwannoma treatment, the choice among treatment modalities is controversial. The first aim of this study was to examine the quality of life of patients with vestibular schwannoma having undergone observation, radiation therapy, or microsurgical resection. The second aim was to examine the relationship between perceived symptoms and quality of life. Last, the association between quality of life and time since treatment was studied. Study Design Cross-sectional study. Setting Tertiary referral center. Subjects and Methods A total of 1208 patients treated for sporadic vestibular schwannoma between 2004 and 2014 were mailed the disease-specific Penn Acoustic Neuroma Quality of Life (PANQOL) questionnaire and additional questions on symptoms associated with vestibular schwannoma. Total and domain scores were calculated and compared among treatment groups. Propensity scores were used, and results were stratified according to tumor size to control for potential confounders. Correlations were calculated to examine the relationship between self-reported symptoms and quality of life, as well as between quality of life and time since treatment. Results Patients with small tumors (≤10 mm) under observation showed a higher PANQOL score when compared with the radiation therapy and microsurgical resection groups. A strong negative correlation was found between self-reported symptoms and quality of life, with balance problems and vertigo having the largest impact. No correlation was found between PANQOL score and time since treatment. Conclusion This study suggests that patients with small vestibular schwannomas experience better quality of life when managed with observation than do patients who have undergone active treatment.

Modal Logics with Counting

NASA Astrophysics Data System (ADS)

Areces, Carlos; Hoffmann, Guillaume; Denis, Alexandre

We present a modal language that includes explicit operators to count the number of elements that a model might include in the extension of a formula, and we discuss how this logic has been previously investigated under different guises. We show that the language is related to graded modalities and to hybrid logics. We illustrate a possible application of the language to the treatment of plural objects and queries in natural language. We investigate the expressive power of this logic via bisimulations, discuss the complexity of its satisfiability problem, define a new reasoning task that retrieves the cardinality bound of the extension of a given input formula, and provide an algorithm to solve it.

Cytokine-Enhanced Vaccine and Interferon-β plus Suicide Gene Therapy as Surgery Adjuvant Treatments for Spontaneous Canine Melanoma.

PubMed

Finocchiaro, Liliana M E; Fondello, Chiara; Gil-Cardeza, María L; Rossi, Úrsula A; Villaverde, Marcela S; Riveros, María D; Glikin, Gerardo C

2015-06-01

We present here a nonviral immunogene therapy trial for canine malignant melanoma, an aggressive disease displaying significant clinical and histopathological overlapping with human melanoma. As a surgery adjuvant approach, it comprised the co-injection of lipoplexes bearing herpes simplex virus thymidine kinase and canine interferon-β genes at the time of surgery, combined with the periodic administration of a subcutaneous genetic vaccine composed of tumor extracts and lipoplexes carrying the genes of human interleukin-2 and human granulocyte-macrophage colony-stimulating factor. Following complete surgery (CS), the combined treatment (CT) significantly raised the portion of local disease-free canine patients from 11% to 83% and distant metastases-free (M0) from 44% to 89%, as compared with surgery-only-treated controls (ST). Even after partial surgery (PS), CT better controlled the systemic disease (M0: 82%) than ST (M0: 48%). Moreover, compared with ST, CT caused a significant 7-fold (CS) and 4-fold (PS) rise of overall survival, and >17-fold (CS) and >13-fold (PS) rise of metastasis-free survival. The dramatic increase of PS metastasis-free survival (>1321 days) and CS recurrence- and metastasis-free survival (both >2251 days) demonstrated that CT was shifting a rapidly lethal disease into a chronic one. In conclusion, this surgery adjuvant CT was able of significantly delaying or preventing postsurgical recurrence and distant metastasis, increasing disease-free and overall survival, and maintaining the quality of life. The high number of canine patients involved in CT (301) and the extensive follow-up (>6 years) with minimal or absent toxicity warrant the long-term safety and efficacy of this treatment. This successful clinical outcome justifies attempting a similar scheme for human melanoma.

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

21 CFR 582.99 - Adjuvants for pesticide chemicals.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Adjuvants for pesticide chemicals. 582.99 Section 582.99 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180...

[Role of Pharmacists in Completion of Adjuvant Cisplatin-Vinorelbine Chemotherapy in Japanese Patients with Non-small Cell Lung Cancer].

PubMed

Morimoto, Yoshihito; Takei, Hidefumi; Tachibana, Keisei; Nakazato, Yoko; Tanaka, Ryota; Nagashima, Yasushi; Watanabe, Kazuhiro; Seki, Reisuke; Shinohara, Takao; Kondo, Haruhiko

2018-01-01

　Adjuvant cisplatin-vinorelbine chemotherapy has been shown to be effective in patients with completely resected non-small cell lung cancer (NSCLC) in several Phase III trials, but not yet in the Japanese population. Pharmacists are expected to assist patients with completion of adjuvant chemotherapy. The aim of this retrospective study was to evaluate the compliance with and safety of adjuvant cisplatin-vinorelbine chemotherapy in Japanese patients and to evaluate the contribution of pharmacists to completion of treatment. Thirty-four patients with NSCLC who received adjuvant cisplatin-vinorelbine chemotherapy at Kyorin University Hospital between January 2006 and June 2015 were reviewed. The treatment schedule comprised cisplatin 80 mg/m 2 on day 1 and vinorelbine 25 mg/m 2 on days 1 and 8 every 3 weeks. Four 3-week cycles were planned. A pharmacist provided guidance to all patients and monitored them for adverse effects thereafter. The pharmacist intervened with advice to doctors as necessary. The 4 cycles were administered in 67.6% of cases. There were no treatment-related deaths. The main grade 3 or 4 toxicities were neutropenia (76.5%) and anorexia (38.2%). The most common reason for discontinuation and dose reduction was anorexia. There were 56 instances of pharmacist intervention. In total, 96.4% of the pharmacist interventions were implemented by doctors, which included administration of an antiemetic on 15 occasions and hot fomentation for prevention of vasculitis on 7 occasions. Adjuvant cisplatin-vinorelbine chemotherapy was tolerated by most patients but was discontinued because of adverse events in some. Pharmacist intervention aids completion of planned chemotherapy and management of treatment-related adverse events.

Novel Adjuvants and Immunomodulators for Veterinary Vaccines.

PubMed

Heegaard, Peter M H; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the vaccine is becoming a reality with our increased understanding of innate and adaptive immune activation. This will allow future vaccines to induce immune reactivity having adequate specificity as well as protective and recallable immune effector mechanisms in appropriate body compartments, including mucosal surfaces. Here we describe these new developments and, when possible, relate new immunological knowledge to the many years of experience with traditional, empirical adjuvants. Finally, some protocols are given for production of emulsion (oil-based) and liposome-based adjuvant/antigen formulations.

SU-F-T-27: A Comparative Case Study Among Four Modalities for the Superficial Treatment of Squamous Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashenafi, M; Koch, N; Peng, J

Purpose: We performed a comparative planning study among High Dose Rate (HDR) brachytherapy, superficial electrons, Volume Modulated Arc Therapy (VMAT), and Helical IMRT (Tomotherapy) for squamous cell carcinoma of the abdominal wall with consideration for the underlining bowel. Methods: A 69-year old female presented with squamous cell carcinoma protruding 8mm beyond the anterior skin surface of the midabdomen was considered for treatment. The patient had a ventral hernia which resulted in the reduction of the abdominal wall thickness and the adjacent small bowel being the dose limiting structure. Four plans were generated using different treatment modalities: a) an enface electronmore » field (eMC, Eclipse v. 11), b) Tomotherapy (HI-Art II v.5.0.5), c) VMAT (Acuros, Eclipse v. 11), and d) HDR using a Freiburg applicator (Oncentra v. 4.3). The following plan objectives were used for all four plans: for the CTV target, V90% ≥90% (61.8Gy2/2).For the small bowel, D0.1cc < 56.2 Gy2/2 was a hard constraint and expressed as a percentage of the prescription for comparison to demonstrate the dose fall-off achieved among the modalities.For HDR, V200% <0.1cc was an additional constraint. Multiple dosimetric parameters, including those listed above, were compared among the four modalities. Results: The HDR plan showed comparable target coverage compared to the Tomotherapy plan and better coverage compared to the electron plan. Small bowel doses (D0.1cc) were lower in HDR plan compared to Tomotherapy, electron, & VMAT plans (88.8%, 89.6%, 90.9%, & 96.6%). Integral dose to the whole body (V5%) was much higher for HDR, VMAT, and Tomotherapy when compared to electron plan by factors of seven, eight, and ten, respectively. After reviewing all treatment modalities, the physician selected HDR owing to better control of the small bowel dose while maintaining adequate target coverage. Conclusion: This case study demonstrated HDR can successfully treat superficial lesions with

Use of Adjuvant 5-Fluorouracil and Radiation Therapy After Gastric Cancer Resection Among the Elderly and Impact on Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strauss, Joshua; Hershman, Dawn L.; Department of Herbert Irving Comprehensive Cancer Center, College of Physicians and Surgeons, Columbia University, New York, NY

2010-04-15

Purpose: In randomized trials patients with resected nonmetastatic gastric cancer who received adjuvant chemotherapy and radiotherapy (chemoRT) had better survival than those who did not. We investigated the effectiveness of adjuvant chemoRT after gastric cancer resection in an elderly general population and its effects by stage. Methods and Materials: We identified individuals in the Surveillance, Epidemiology, and End Results-Medicare database aged 65 years or older with Stage IB through Stage IV (M0) gastric cancer, from 1991 to 2002, who underwent gastric resection, using multivariate modeling to analyze predictors of chemoRT use and survival. Results: Among 1,993 patients who received combinedmore » chemoRT or no adjuvant therapy after resection, having a later year of diagnosis, having a more advanced stage, being younger, being white, being married, and having fewer comorbidities were associated with combined treatment. Among 1,476 patients aged less than 85 years who survived more than 4 months, the 313 who received combined treatment had a lower mortality rate (hazard ratio, 0.83; 95% confidence interval, 0.71-0.98) than the 1,163 who received surgery alone. Adjuvant therapy significantly reduced the mortality rate for Stages III and IV (M0), trended toward improved survival for Stage II, and showed no benefit for Stage IB. We observed trends toward improved survival in all age categories except 80 to 85 years. Conclusions: The association of combined adjuvant chemoRT with improved survival in an overall analysis of Stage IB through Stage IV (M0) resected gastric cancer is consistent with clinical trial results and suggests that, in an elderly population, adjuvant chemoradiotherapy is effective. However, our observational data suggest that adjuvant treatment may not be effective for Stage IB cancer, is possibly appropriate for Stage II, and shows significant survival benefits for Stages III and IV (M0) for those aged less than 80 years.« less

Low-intensity ultrasound adjuvant therapy: enhancement of doxorubicin-induced cytotoxicity and the acoustic mechanisms involved.

PubMed

Kondo, Takashi; Yoshida, Toru; Ogawa, Ryohei; Hassan, Mariame A; Furusawa, Yukihiro; Zhao, Qing-Li; Watanabe, Akihiko; Morii, Akihiro; Feril, Loreto B; Tachibana, Katsuro; Kitagawa, Hiroshi; Tabuchi, Yoshiaki; Takasaki, Ichiro; Shehata, Mohammad H; Kudo, Nobuki; Tsukada, Kazuhiro

2009-06-01

In this study, the effects of low-intensity pulsed ultrasound (LIU) as an adjuvant to doxorubicin (DOX) treatment was further investigated in comparison to hyperthermia as another widely used adjuvant. The effects were compared with respect to cell killing and apoptosis induction in U937 cells. Human primary liver cancer (PLC) cells were also used to evaluate the effects of the combinations. The use of an echo contrast agent was investigated for further enhancement of cytotoxicity. Finally, the acoustic mechanisms involved were investigated. The effects of different treatment regimens on cell viability were determined using the Trypan blue dye-exclusion test. Apoptosis induction was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. The mechanistic study involved electron paramagnetic spin trapping for detecting free radical formation as an indicator of the occurrence of inertial cavitation and spectrophotometry for sucrose hydrolysis as an indicator for noncavitational effects. The combination treatments exerted synergistic effects on cytotoxicity depending on the acoustic conditions used. The use of LIU as an adjuvant to DOX treatment was shown to be superior to the use of hyperthermia as an adjuvant. Moreover, the combination seems to be promising for other cancer types provided that the acoustic conditions are properly selected with respect to drug concentration. The key ultrasound mechanism responsible for the synergism observed was shown to be the production of free radicals by inertial cavitation. Non-cavitational forces were also shown to contribute to the effect. This study is motivating to engage in in vivo research with various cancer types as a step toward clinical applicability and is emphasizing on the importance of developing therapeutic protocols for setting LIU parameters with respect to other therapeutic conditions.

Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

PubMed

Zaenger, David; Rabatic, Bryan M; Dasher, Byron; Mourad, Waleed F

2016-04-01

Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions. Copyright © 2016 Elsevier Inc. All rights reserved.

Cost analysis of adjuvant management strategies in early stage (stage I) testicular seminoma

PubMed Central

Cox, John A; Gajjar, Shefali R; Lanni, Thomas B; Swanson, Todd A

2015-01-01

Background Acceptable post-orchiectomy adjuvant therapy strategies for stage I seminoma patients include surveillance, para-aortic radiation therapy (RT), dog-leg RT, and a single cycle of carboplatin. The required follow-up recommendations were amended by the National Comprehensive Cancer Network (NCCN) in 2012. Given a cause-specific survival of nearly 100%, a closer analysis of the reimbursement for each treatment strategy is warranted. Methods NCCN guidelines were used to design treatment plans for each acceptable adjuvant treatment strategy. Follow-up charges were generated for 10 years based on 2012 (version 1.2012; unchanged in current version 1.2013) and 2011 NCCN (version 2.2011) surveillance recommendations. The 2012 Medicare reimbursement rates were used to calculate each treatment strategy and incremental cost-effectiveness ratios to compare the treatment options. Results Under the current NCCN follow-up recommendations, the total reimbursements generated over 10 years of surveillance, para-aortic RT, dog-leg RT, and carboplatin were $10,643, $11,678, $9,662, and $10,405, respectively. This is compared with the reimbursements as per the 2011 NCCN recommendations: $20,986, $11,517, $9,394, and $20,365 respectively. Factoring the rates of relapse into a salvage model, observation was found to be more costly and less effective ($–1,831, $−7,318, $–7,010) in the adjuvant management of stage I seminoma patients Conclusion Based on incremental cost-effectiveness ratios, para-aortic RT, dog-leg RT, and carboplatin are cost-effective options for the treatment of stage I seminoma when compared with observation; however, surveillance could potentially spare as many as 80%–85% of men diagnosed with stage I seminoma from additional therapy after radical inguinal orchiectomy. Such cost and reimbursement analyses are becoming increasingly relevant, but are not meant to usurp sound clinical judgment. Further studies are required to validate these findings

Vaccine Adjuvants: from 1920 to 2015 and Beyond

PubMed Central

Di Pasquale, Alberta; Preiss, Scott; Tavares Da Silva, Fernanda; Garçon, Nathalie

2015-01-01

The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190

Transoral Resection of Human Papillomavirus (HPV)-Positive Squamous Cell Carcinoma of the Oropharynx: Outcomes with and Without Adjuvant Therapy.

PubMed

Jackson, Ryan S; Sinha, Parul; Zenga, Joseph; Kallogjeri, Dorina; Suko, Jasmina; Martin, Eliot; Moore, Eric J; Haughey, Bruce H

2017-11-01

With the rise of oropharyngeal squamous cell carcinoma associated with human papillomavirus (HPV), appropriate treatment strategies continue to be tailored toward minimizing treatment while preserving oncologic outcomes. This study aimed to compare the outcomes for those undergoing transoral resection with or without adjuvant therapy for HPV-related oropharyngeal carcinoma. A case-match cohort analysis was performed at two institutions on patients with HPV-related oropharyngeal squamous cell carcinoma. All the subjects underwent transoral surgery and neck dissection. The patients treated with surgery alone were matched 1:1 to those treated with surgery and adjuvant therapy using two groups identified as confounders: T-stage (T1/2 or T3/4) and number of pathologically positive lymph nodes (≤4 or >4). The study identified 105 matched pairs, with a median follow-up period of 42 months (range 3.1-102.3 months). The patients were staged as T1/T2 (86%) or T3/4 (14%). Each group had five patients with more than four positive lymph nodes. Adjuvant therapy significantly improved disease-free survival (hazard ratio [HR] 0.067; 95% confidence interval [CI] 0.01-0.62) and was associated with a lower risk of local and regional recurrence (risk ratio [RR] 0.096; 95% CI 0.02-0.47). No difference in disease-specific survival (HR 0.22; 95% CI 0.02-2.57) or overall survival (HR 0.18; 95% CI 0.01-2.4) was observed with the addition of adjuvant therapy. The risk of the gastrostomy tube was higher for those receiving adjuvant therapy (RR 7.3; 95% CI 2.6-20.6). Transoral surgery is an effective approach for the treatment of HPV-related oropharyngeal carcinoma. The addition of adjuvant therapy appears to decrease the risk of recurrence and improve disease-free survival but may not significantly improve overall survival.

Effects of Formulated Glyphosate and Adjuvant Tank Mixes on Atomization from Aerial Application Flat Fan Nozzles

DTIC Science & Technology

2012-01-01

Bradley K. Fritz,1 W. Clint Hoffmann,1 and W. E. Bagley2 Effects of Formulated Glyphosate and Adjuvant Tank Mixes on Atomization from Aerial...Application Flat Fan Nozzles REFERENCE: Fritz, Bradley K., Hoffmann, W. Clint, and Bagley, W. E., “Effects of Formulated Glyphosate and Adjuvant Tank Mixes on...factors. Twelve spray-solution treatments were evaluated, ten of which contained a formulated glyphosate product and nine of these con- tained an

Biological effects of Corynebacterium parvum. IV. Adjuvant and inhibitory activities on B lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howard, J.G.; Christie, G.H.; Scott, M.T.

1973-05-01

The PFC response to the thymus-independent antigen SIII (type 3 pneumococcal polysaccharide) was amplified in mice injected 4 days previously with killed Corynebacterium parvum. This adjuvant activity was demonstrable with high (2 to 50 mu g) but not low (0.1 to 0.5 mu g) doses of SIII. Induction of tolerance was unaffected. Depression of the response resulted from simultaneous injection of SIII with either C. parvum or Bordetella pertussis, while prior treatment with the latter was without effect. Responsiveness to SIII was transiently but potently suppressed in spleen cells transferred into lethally irradiated, C. parvum pretreated mice. Although C. parvummore » is an effective B cell adjuvant, other data imply that it acts indirectly on these lymphocytes. It is argued that both adjuvant and suppressive activities of C. parvum on the B cell response to SIII are most probably mediated by activated macrophages. (auth)« less

Biological effects of Corynebacterium parvum. IV. Adjuvant and inhibitory activities on B lymphocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howard, J.G.; Christie, G.H.; Scott, M.T.

1973-05-01

The PFC response to the thymus-independent antigen SIII(type 3 pneumococcal polysaccharide) was amplified in mice injected 4 days previously with killed Corynebacterium parvum. This adjuvant activity was demonstrable with high (2 to 50 mu g) but not low (0.1 to 0.5 mu g) doses of SIII. Induction of tolerance was unaffected. Depression of the response resulted from simultaneous injection of SIII with either C. parvum or Bordetella pertussis, while prior treatment with the latter was without effect. Responsiveness to SIII was transiently but potently suppressed in spleen cells transferred into lethally irradiated, C. parvum pretreated mice. Although C. parvum ismore » an effective B cell adjuvant, other data imply that it acts indirectly on these iymphocytes. It is argued that both adjuvant and suppressive activities of C. parvum on the B cell response to SIII are most probably mediated by activated macrophages. (auth)« less

Rabies virus vaccine as an immune adjuvant against cancers and glioblastoma: new studies may resurrect a neglected potential.

PubMed

Altinoz, M A; Guloksuz, S; Elmaci, I

2017-07-01

To review the literature about the use of Rabies Virus-Vaccine (RV-V) as an anticancer immunotherapeutic modality in the light of recent findings. The literature search in relevant databases with the following key words: Rabies virus, cancer, remission. Remissions occured following RV-V injections in patients with cervical cancer and melanoma. Pilot clinical studies showed that RV-V injections enhanced survival in glioblastoma patients, which is supported by findings in GL261 mouse glioma model. If public health studies demonstrate protective role of RV-V against certain types of cancers, it can be benefitted as a novel immune adjuvant in clinic.

TU-FG-201-03: Automatic Pre-Delivery Verification Using Statistical Analysis of Consistencies in Treatment Plan Parameters by the Treatment Site and Modality

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, S; Wu, Y; Chang, X

Purpose: A novel computer software system, namely APDV (Automatic Pre-Delivery Verification), has been developed for verifying patient treatment plan parameters right prior to treatment deliveries in order to automatically detect and prevent catastrophic errors. Methods: APDV is designed to continuously monitor new DICOM plan files on the TMS computer at the treatment console. When new plans to be delivered are detected, APDV checks the consistencies of plan parameters and high-level plan statistics using underlying rules and statistical properties based on given treatment site, technique and modality. These rules were quantitatively derived by retrospectively analyzing all the EBRT treatment plans ofmore » the past 8 years at authors’ institution. Therapists and physicists will be notified with a warning message displayed on the TMS computer if any critical errors are detected, and check results, confirmation, together with dismissal actions will be saved into database for further review. Results: APDV was implemented as a stand-alone program using C# to ensure required real time performance. Mean values and standard deviations were quantitatively derived for various plan parameters including MLC usage, MU/cGy radio, beam SSD, beam weighting, and the beam gantry angles (only for lateral targets) per treatment site, technique and modality. 2D-based rules of combined MU/cGy ratio and averaged SSD values were also derived using joint probabilities of confidence error ellipses. The statistics of these major treatment plan parameters quantitatively evaluate the consistency of any treatment plans which facilitates automatic APDV checking procedures. Conclusion: APDV could be useful in detecting and preventing catastrophic errors immediately before treatment deliveries. Future plan including automatic patient identify and patient setup checks after patient daily images are acquired by the machine and become available on the TMS computer. This project is supported by

Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: a Dutch TEAM trial analysis.

PubMed

van Nes, Johanna G H; Beex, Louk V A M; Seynaeve, Caroline; Putter, Hein; Sramek, Alexandr; Lardenoije, Susanne; Duijm-de Carpentier, Marjolijn; Van Rongen, Inge; Nortier, Johan W R; Zonderland, Harmien M; van de Velde, Cornelis J H

2015-03-01

Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Analogue mammograms of selected TEAM participants before start, and after one and two (and if available after three) years of adjuvant endocrine therapy were collected centrally and reviewed. Study endpoints were change in breast density over time, and correlations between breast density and locoregional recurrence (LRR), distance recurrence (DR), and contralateral breast cancer (CBC). Mammograms of 378 patients (181 tamoxifen, 197 exemestane) were included in the current per protocol analyses. Baseline breast density was low (breast density score<50% in 75% of patients) and not different between patients randomised to exemestane or tamoxifen (coefficient 0.16, standard error 0.17). Breast density did not change during treatment in exemestane (p=0.25) or tamoxifen users (p=0.59). No relation was observed between breast density and the occurrence of a LRR [hazards ratio (HR) 0.87, 95% CI 0.45-1.68, p=0.67], a DR (HR 1.02, 95% CI 0.77-1.35, p=0.90), or CBC (HR 1.31, 95% CI 0.63-2.72, p=0.48). The in general low breast density score in early postmenopausal breast cancer patients did not substantially change over time, and this pattern was not different between tamoxifen and exemestane users. Breast density was not a predictive marker for efficacy of adjuvant endocrine therapy.

Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens against highly pathogenic avian influenza virus.

PubMed

Lone, Nazir Ahmed; Spackman, Erica; Kapczynski, Darrell

2017-06-08

Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the best formulations for chickens, vaccines were prepared with beta-propiolactone (BPL) inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially available or experimental adjuvants. Each vaccine formulation was evaluated for immunogenicity in chickens. Challenge studies with an antigenically homologous strain of HPAIV were conducted to compare protection against mortality and measure reductions in virus levels in oral swabs. The four best adjuvants from the studies with BPL inactivated antigen were selected and tested identically, but with vaccines prepared from formalin inactivated virus. Mineral and vegetable oil based adjuvants generally induced the highest antibody titers with 100% seroconversion by 3weeks post vaccination. Chitosan induced positive antibody titers in 100% of the chickens, but the titers were significantly lower than those of most of the oil based adjuvants. Antibody levels from calcium phosphate and alginate adjuvanted groups were similar to those of non-adjuvanted virus. All groups that received adjuvanted vaccines induced similar levels of protection against mortality (0-20%) except the groups vaccinated with calcium phosphate adjuvanted vaccines, where mortality was similar (70%) to groups that received non-adjuvanted inactivated virus or no vaccine (60-100% mortality). Virus shedding in oral swabs was variable among the treatment groups. Formalin inactivated vaccine induced similar antibody titers and protection against challenge compared to BPL inactivated vaccine groups. These studies support the use of oil adjuvanted vaccines for use in the poultry industry for control for AIV. Published by Elsevier Ltd.

Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects.

PubMed

Vyas, Purvi; Thakar, A B; Baghel, M S; Sisodia, Arvind; Deole, Yogesh

2010-10-01

Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy.

Use of New Treatment Modalities for Non-small Cell Lung Cancer Care in the Medicare Population

PubMed Central

Vest, Michael T.; Herrin, Jeph; Soulos, Pamela R.; Decker, Roy H.; Tanoue, Lynn; Michaud, Gaetane; Kim, Anthony W.; Detterbeck, Frank; Morgensztern, Daniel

2013-01-01

Background: Many older patients with early stage non-small cell lung cancer (NSCLC) do not receive curative therapy. New surgical techniques and radiation therapy modalities, such as video-assisted thoracoscopic surgery (VATS), potentially allow more patients to receive treatment. The adoption of these techniques and their impact on access to cancer care among Medicare beneficiaries with stage I NSCLC are unknown. Methods: We used the Surveillance, Epidemiology and End Results-Medicare database to identify patients with stage I NSCLC diagnosed between 1998 and 2007. We assessed temporal trends and created hierarchical generalized linear models of the relationship between patient, clinical, and regional factors and type of treatment. Results: The sample comprised 13,458 patients with a mean age of 75.7 years. The proportion of patients not receiving any local treatment increased from 14.6% in 1998 to 18.3% in 2007. The overall use of surgical resection declined from 75.2% to 67.3% (P < .001), although the proportion of patients undergoing VATS increased from 11.3% to 32.0%. Similarly, although the use of new radiation modalities increased from 0% to 5.2%, the overall use of radiation remained stable. The oldest patients were less likely to receive surgical vs no treatment (OR, 0.12; 95% CI, 0.09-0.16) and more likely to receive radiation vs surgery (OR, 13.61; 95% CI, 9.75-19.0). Conclusion: From 1998 to 2007, the overall proportion of older patients with stage I NSCLC receiving curative local therapy decreased, despite the dissemination of newer, less-invasive forms of surgery and radiation. PMID:23187634

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma.

PubMed

Weber, Jeffrey; Mandala, Mario; Del Vecchio, Michele; Gogas, Helen J; Arance, Ana M; Cowey, C Lance; Dalle, Stéphane; Schenker, Michael; Chiarion-Sileni, Vanna; Marquez-Rodas, Ivan; Grob, Jean-Jacques; Butler, Marcus O; Middleton, Mark R; Maio, Michele; Atkinson, Victoria; Queirolo, Paola; Gonzalez, Rene; Kudchadkar, Ragini R; Smylie, Michael; Meyer, Nicolas; Mortier, Laurent; Atkins, Michael B; Long, Georgina V; Bhatia, Shailender; Lebbé, Celeste; Rutkowski, Piotr; Yokota, Kenji; Yamazaki, Naoya; Kim, Tae M; de Pril, Veerle; Sabater, Javier; Qureshi, Anila; Larkin, James; Ascierto, Paolo A

2017-11-09

Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population. At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment. Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade

Technological Advances in the Treatment of Cancer: Combining Modalities to Optimize Outcomes.

PubMed

Wong, Eric T; Toms, Steven A; Ahluwalia, Manmeet S

2015-11-01

The anticancer treatment modality tumor treating fields (TTFields; Optune, Novocure) use the lower frequency range of the electromagnetic spectrum to destroy tumor cells during mitosis. This treatment has been evaluated in several trials of patients with glioblastoma. In these patients, TTFields are delivered through 4 transducer arrays applied to the scalp. In a phase 3 clinical trial of patients with recurrent glioblastoma, TTFields were as effective as chemotherapy, and were associated with fewer and milder systemic toxicities. Data from a phase 3 trial in newly diagnosed glioblastoma suggested that the addition of TTFields to postoperative radiation therapy and chemotherapy represents an important advance in the management of newly diagnosed glioblastoma. Ongoing clinical trials are investigating the efficacy and safety of TTFields in other tumor types, including pancreatic cancer, mesothelioma, ovarian cancer, and non–small cell lung cancer. Other recent advances in the management of cancer have been seen with immunomodulatory therapy, including immune checkpoint inhibitors. Further study will be necessary to evaluate whether TTFields will enhance or impair other established and newly emerging therapies.

A New Modality for Cancer Treatment--Nanoparticle Mediated Microwave Induced Photodynamic Therapy.

PubMed

Yao, Mengyu; Ma, Lun; Li, Lihua; Zhang, Junying; Lim, Rebecca; Chen, Wei; Zhang, Yu

2016-10-01

Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality for cancer treatment. However, due to poor tissue penetration by light, photodynamic therapy has rarely been used for deeply situated tumors. This problem can be solved if photosensitizers are activated by microwaves (MW) that are able to penetrate deeply into tissues. Here, for the first time, we report microwave-induced photodynamic therapy and exploit copper cysteamine nanoparticles as a new type of photosensitizer that can be activated by microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The heating effects and the release of copper ions from Cu-Cy upon MW stimulation are the main mechanisms for the generation of reactive oxygen species that are lethal bullets for cancer destruction. The copper cysteamine nanoparticle-based microwave-induced photodynamic therapy opens a new door for treating cancer and other diseases.

Bacterial vaginosis: Etiology and modalities of treatment—A brief note

PubMed Central

Kumar, Nikhil; Behera, Beauty; Sagiri, Sai S.; Pal, Kunal; Ray, Sirsendu S.; Roy, Saroj

2011-01-01

A large women population of the world is suffering from a vaginal infection commonly known as bacterial vaginosis. The disease is associated with the decrease in the lactobacilli count in the vagina. Till date, there is a lack of full proof treatment modalities for the cure of the disease. The treatment includes the use of antimicrobials and/or acidifying agents and probiotics, either separately or in combination. This note discusses about the etiology and the various present-day modalities of treatment of bacterial vaginosis. PMID:22219582

Polyphenolics isolated from virgin coconut oil inhibits adjuvant induced arthritis in rats through antioxidant and anti-inflammatory action.

PubMed

Vysakh, A; Ratheesh, M; Rajmohanan, T P; Pramod, C; Premlal, S; Girish kumar, B; Sibi, P I

2014-05-01

We evaluated the protective efficacy of the polyphenolic fraction from virgin coconut oil (PV) against adjuvant induced arthritic rats. Arthritis was induced by intradermal injection of complete Freund's adjuvant. The activities of inflammatory, antioxidant enzymes and lipid peroxidation were estimated. PV showed high percentage of edema inhibition at a dose of 80mg/kg on 21st day of adjuvant arthritis and is non toxic. The expression of inflammatory genes such as COX-2, iNOS, TNF-α and IL-6 and the concentration of thiobarbituric acid reactive substance were decreased by treatment with PV. Antioxidant enzymes were increased and on treatment with PV. The increased level of total WBC count and C-reactive protein in the arthritic animals was reduced in PV treated rats. Synovial cytology showed that inflammatory cells and reactive mesothelial cells were suppressed by PV. Histopathology of paw tissue showed less edema formation and cellular infiltration on supplementation with PV. Thus the results demonstrated the potential beneficiary effect of PV on adjuvant induced arthritis in rats and the mechanism behind this action is due to its antioxidant and anti-inflammatory effects. Copyright © 2014 Elsevier B.V. All rights reserved.

Adjuvant radiotherapy after transoral laser microsurgery for advanced squamous carcinoma of the head and neck

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pradier, Olivier; Christiansen, Hans; Schmidberger, Heinz

Purpose: To evaluate the efficacy of an adjuvant radiotherapy after transoral laser microsurgery for advanced squamous cell carcinoma of the head and neck and to show that a less invasive surgery with organ preservation in combination with radiotherapy is an alternative to a radical treatment. Patients and Methods: Between 1987 and 2000, 208 patients with advanced squamous cell carcinoma of the head and neck were treated with postoperative radiotherapy after surgical CO{sub 2} laser resection. Primary sites included oral cavity, 38; oropharynx, 88; larynx, 36; hypopharynx, 46. Disease stages were as follows: Stage III, 40 patients; Stage IV, 168 patients.more » Before 1994, the treatment consisted of a split-course radiotherapy with carboplatinum (Treatment A). After 1994, the patients received a conventional radiotherapy (Treatment B). Results: Patients had 5-year locoregional control and disease-specific survival (DSS) rates of 68% and 48%, respectively. The 5-year DSS was 70% and 44% for Stages III and IV, respectively (p = 0.00127). Patients treated with a hemoglobin level greater or equal to 13.5 g/dL before radiotherapy had a 5-year DSS of 55% as compared with 39% for patients treated with a hemoglobin level greater than 13.5 g/dL (p = 0.0054). Conclusion: In this series of patients with advanced head-and-neck tumors, transoral laser surgery in combination with adjuvant radiotherapy resulted in locoregional control and DSS rates similar to those reported for radical surgery followed by radiotherapy. Treatment B has clearly been superior to Treatment A. A further improvement of our treatment regimen might be expected by the combination of adjuvant radiotherapy with concomitant platinum-based chemotherapy.« less

Performance characteristics of a conformal ultra-wideband multilayer applicator (CUMLA) for hyperthermia in veterinary patients: a pilot evaluation of its use in the adjuvant treatment of non-resectable tumours.

PubMed

Smrkovski, O A; Koo, Y; Kazemi, R; Lembcke, L M; Fathy, A; Liu, Q; Phillips, J C

2013-03-01

Performance and clinical characteristics of a novel hyperthermia antenna operating at 434 MHz were evaluated for the adjuvant treatment of locally advanced superficial tumours in cats, dogs and horses. Electromagnetic simulations were performed to determine electric field characteristics and compared to simulations for a flat microwave antenna with similar dimensions. Simulation results show a reduced skin surface and backfield irradiation and improved directional irradiation (at broadside) compared to a flat antenna. Radiated power and penetration is notably increased with a penetration depth of 4.59 cm compared to 2.74 cm for the flat antenna. Clinical use of the antenna was then evaluated in six animals with locoregionally advanced solid tumours receiving adjuvant chemotherapy. During clinical applications, therapeutic temperatures were achieved at depths ≥4 cm. Objective responses were seen in all patients; tissue toxicity in one case limited further therapy. This antenna provides compact, efficient, focused and deep-penetrating clinical hyperthermia for the treatment of solid tumours in veterinary patients. © 2011 Blackwell Publishing Ltd.

Singapore Cancer Network (SCAN) Guidelines for Adjuvant Chemotherapy in Resected Non-Small Cell Lung Cancer.

PubMed

2015-10-01

The SCAN lung cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for the use of adjuvant systemic therapy for non-small cell lung cancer in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Comprehensive Cancer Network (2014), European Society of Medical Oncology (2014), National Institute of Clinical Excellence (2012), Scottish Intercollegiate Guidelines Network (2014), and the Cancer Care Council Australia (2012). Recommendations on the selection of patients, chemotherapy regimen, treatment for stage I disease, treatment for positive margins and treatment options for pN2 disease with negative margins were produced. These adapted guidelines form the SCAN Guidelines 2015 for adjuvant systemic therapy of non-small cell lung cancer.

The short-term safety of adjuvant paclitaxel plus trastuzumab - A single centre experience.

PubMed

Ates, Ozturk; Sunar, Veli; Aslan, Alma; Karatas, Fatih; Sahin, Suleyman; Altundag, Kadri

2017-01-01

HER2-amplified breast cancer (BC) has a poor prognosis. The combination of trastuzumab with chemotherapy in the adjuvant setting decreases recurrence and improves overall survival in HER2-positive BC. However, the role of adjuvant treatment in patients with HER2-amplified small BC without lymph node involvement is still under debate. The purpose of this study was to investigate the safety of adjuvant paclitaxel and trastuzumab (APT) in this group of patients. A total of 87 operated early BC patients without lymph node involvement (N0) were treated with APT for 12 weeks followed by trastuzumab alone for a total of 9 months. Clinicopathological features and adverse events were analyzed. The median patient age was 50 years (range 28- 82), and 51% of them were postmenopausal. The median tumor diameter was 2.4 cm (range 0.5-6), with 51% of the patients having tumor size between 2 and 3 cm. Eighty-one percent of patients had invasive ductal carcinoma (IDC), and 64% had grade 3 tumors. Adjuvant hormone therapy and adjuvant radiotherapy were administered to 65 and 54% of patients, respectively. At a median follow up of 13 months (range 6-38), one patient (1.1%, 95% CI 0-3.4) experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) and 3 patients (3.4%, 95% CI 0-6.9) experienced grade 3 neuropathy. APT appears to be a safe combination in early-stage, HER2-amplified and node-negative BC.

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

PubMed

Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

2016-11-01

To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Four cycles of paclitaxel and carboplatin as adjuvant treatment in early-stage ovarian cancer: a six-year experience of the Hellenic Cooperative Oncology Group

PubMed Central

Bamias, Aristotle; Papadimitriou, Christos; Efstathiou, Eleni; Rodolakis, Alexandros; Vlahos, Georgios; Voulgaris, Zannis; Bozas, Georgios; Fountzilas, Georgios; Aravantinos, Gerassimos; Razis, Evagelia; Gika, Dimitra; Dimopoulos, Meletios A

2006-01-01

Background Surgery can cure a significant percentage of ovarian carcinoma confined to the pelvis. Nevertheless, there is still a 10–50% recurrence rate. We administered paclitaxel/carboplatin as adjuvant treatment in early-stage ovarian carcinoma. Methods Patients with stages Ia or Ib, Grade 2 or 3 and Ic to IIb (any grade) were included. Patients were treated with 4 cycles of Paclitaxel 175 mg/m2 and Carboplatin [area under the curve (AUC) 6 (Calvert Formula)] every 3 weeks. Results Sixty-nine patients with no residual disease following cytoreductive surgery and minimal or modified surgical staging were included in this analysis. Grade 3 or 4 neutropenia occured in 29.9% of patients, while neutropenic fever was reported in 4.5%. Neurotoxicity (all Grade 1 or 2) was reported in 50% of cases. Median follow-up was 62 months. 5-year overall survival (OS) and relapse-free survival (RFS) were: 87% (95% confidence intervals [CI]: 78–96) and 79% (95% CI: 69–89), respectively. Significantly fewer patients with stages Ic-IIb and tumor grade 2 or 3 achieved a 5-year RFS than patients with only one of these two factors (73% vs 92%, p = 0.03). Conclusion Paclitaxel/Carboplatin chemotherapy is a safe and effective adjuvant treatment in early-stage ovarian carcinoma. Patients with stages Ic-IIb and tumor grade 2 or 3 may benefit from more extensive treatment. PMID:16999858

Assessing the Real-World Cost-Effectiveness of Adjuvant Trastuzumab in HER-2/neu Positive Breast Cancer

PubMed Central

Hedden, Lindsay; O'Reilly, Susan; Lohrisch, Caroline; Chia, Stephen; Speers, Caroline; Kovacic, Laurel; Taylor, Suzanne

2012-01-01

Background. Among women with surgically removed, high-risk HER-2/neu-positive breast cancer, trastuzumab has demonstrated significant improvements in disease-free and overall survival. The objective of this study is to evaluate the cost-effectiveness of the currently recommended 12-month adjuvant protocol of trastuzumab using a Markov modeling approach and real-world cost data. Methods. A 10-health-state Markov model tracked patients' quarterly transitions between health states in the local and advanced states of breast cancer. Clinical data were obtained from the joint analysis of the National Surgical Adjuvant Breast and Bowel Project and North Central Cancer Treatment Group, as well as from the metastatic study conducted by Norum et al. Clinical outcomes were adjusted for quality of life using utility estimates published in a systematic review. Real cost data were obtained from the British Columbia Cancer Agency and were evaluated from a payer perspective. Costs and utilities were discounted at 5% per year, respectively, for a 28-year time horizon. Results. In the base case analysis, treatment with a 12-month adjuvant trastuzumab regimen resulted in a gain of 1.38 quality-adjusted life years or 1.17 life years gained at a cost of $18,133 per patient. Thus, the cost per QALY gained for the base case is $13,095. Cost per LYG is $15,492. Conclusions. Over the long term, treatment of HER-2/neu mutation positive breast cancer with a 12-month protocol of trastuzumab in the adjuvant setting is predicted to be cost-effective in a Canadian context. PMID:22302231

Mental Health Disorder Therapeutic Modalities Modified for the GMS

PubMed Central

Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

2017-01-01

Background: Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Methods: The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Results: Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. Conclusion: The

Adjuvants for veterinary vaccines--types and modes of action.

PubMed

Gerdts, Volker

2015-01-01

Adjuvants are used to improve the immune response to vaccines. Formulation with adjuvants can result in an earlier onset of immunity, an overall stronger immune response, a specific type of immunity, or a longer duration of immunity to the vaccine. Adjuvants were discovered empirically, and for decades, have been used in both humans and animals without understanding the mechanisms of action. With an improved understanding of the immune system, and in particular the interplay between innate and adaptive immunity, we are now getting better insight into the function of adjuvants. As a result, new adjuvants are being developed that are safe and highly effective for common use in humans and animals, as well as for use in high risk populations such as immunocompromised animals, neonates or very old animals. Furthermore, adjuvants can help to reduce the amount of antigen needed in the vaccine, increase the stability of the vaccine and enable alternatiye administration routes such as needle-free delivery of the vaccine. Here, I will provide an over view of the existing adjuvant technologies for veterinary vaccines and provide an outlook into some of the new technologies in preclinical and clinical development.

An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

PubMed

Fox, Christopher B; Haensler, Jean

2013-07-01

With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

Computational prediction of multidisciplinary team decision-making for adjuvant breast cancer drug therapies: a machine learning approach.

PubMed

Lin, Frank P Y; Pokorny, Adrian; Teng, Christina; Dear, Rachel; Epstein, Richard J

2016-12-01

Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines. Machine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p < 0.01, representing 43% and 53% variations from ESMO/NCCN guidelines, respectively). Using ten-fold cross-validation, the best classifiers achieved areas under the receiver operating characteristic curve (AUC) of 0.940 for chemotherapy (95% C.I., 0.922-0.958), 0.899 for the endocrine therapy (95% C.I., 0.880-0.918), and 0.977 for trastuzumab therapy (95% C.I., 0.955-0.999) respectively. Overall, bootstrap aggregated classifiers performed better among all evaluated machine learning models. A machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions

Overview of Vaccine Adjuvants: Introduction, History, and Current Status.

PubMed

Shah, Ruchi R; Hassett, Kimberly J; Brito, Luis A

2017-01-01

Adjuvants are included in sub-unit or recombinant vaccines to enhance the potency of poorly immunogenic antigens. Adjuvant discovery is as complex as it is a multidiscplinary intersection of formulation science, immunology, toxicology, and biology. Adjuvants such as alum, which have been in use for the past 90 years, have illustrated that adjuvant research is a methodical process. As science advances, new analytical tools are developed which allows us to delve deeper into the various mechanisms that generates a potent immune response. Additionally, these new techniques help the field learn about our existing vaccines and what makes them safe, and effective, allowing us to leverage that in the next generation of vaccines. Our goal in this chapter is to define the concept, need, and mechanism of adjuvants in the vaccine field while describing its history, present use, and future prospects. More details on individual adjuvants and their formulation, development, mechanism, and use will be covered in depth in the next chapters.

Surgery versus radiation therapy as single-modality treatment of tonsillar fossa carcinoma: the Roswell Park Cancer Institute experience (1971-1991).

PubMed

Hicks, W L; Kuriakose, M A; Loree, T R; Orner, J B; Schwartz, G; Mullins, A; Donaldson, C; Winston, J M; Bakamjian, V Y

1998-07-01

To compare the efficacy and treatment outcomes in patients with tonsillar fossa cancer using surgery or radiation as a single modality therapy. From 1971 to 1991 239 patients with oral pharyngeal cancer were treated at Roswell Park Cancer Institute. Of these patients 90 had tonsillar carcinoma. Seventy-six of these patients received either surgery (SA) (n = 56) or radiation therapy (RA) (n = 20) as single-modality therapy and are the subject of this review. All patients in the radiation arm of this review were surgical candidates who declined primary surgical therapy. Sixty-three percent of the SA and 80% of the RA treatment groups presented with either stage III or stage IV disease (P < or = .05). Forty-seven percent of the SA group and 52% of the RA patients had clinically positive regional disease at initial presentation. There was a predictable pattern of nodal presentation, with level II the most frequently involved region. The rate of occult metastasis was 27% and was evenly distributed between T1 and T4 disease. The overall local control rate in the SA group was 75%, compared with 60% in the RA group (P value was not significant). The disease-specific survival (all stages) was 61% in the SA group and 37% in the RA group (P < or = .05). The disease-free survival for stage III and stage IV disease in the SA group was 47% and in the RA group 27% (P < or = .05). Survival measured against clinical response to radiation therapy, in complete responders (all stages) was 83%; by contrast there were no survivors past 24 months in the partial response group (P < or = .001). The results from this study suggest that for early disease (stage I/II), surgery or radiation therapy as single-modality treatment is equally effective. For advanced disease radiation therapy is inferior to surgery as a single-modality treatment, as measured by ultimate survival and the local control of disease. There is, however, a subset of patients with advanced disease who respond to radiation

Changes in Weight and Body Composition Among Women With Breast Cancer During and After Adjuvant Treatment: A Prospective Follow-up Study.

PubMed

Pedersen, Birgith; Delmar, Charlotte; Bendtsen, Mette Dahl; Bosaeus, Ingvar; Carus, Andreas; Falkmer, Ursula; Groenkjaer, Mette

Antineoplastic adjuvant treatment for breast cancer can cause changes in women's weight and body composition and influence their general health and survival. The aim of this study is to investigate the extent and patterns of change in weight and body composition after current standard adjuvant antineoplastic treatment for breast cancer. Data on weight and body composition from 95 women with breast cancer Stage I to III were obtained during 18 months on a bioelectric impedance analyzer. Changes and odds ratio (OR) were calculated by a linear mixed model and logistic regression. At 18 months, there was an increase in weight of 0.9 kg (95% confidence interval [CI], 0.3-1.5; P = .003) and an average positive association of 0.35 kg/cm increased waist circumference (95% CI, 0.29-0.42 kg; P < .0001). Relative weight changes ranged from -12.7% to 20.5%. Weight gains related to increased body fat were observed mainly in premenopausal women receiving chemotherapy (1.4 kg; 95% CI, 0.4-2.4; P = .007). For menopausal status, OR was 2.9 (95% CI, 1.14-7.1; P = .025), and for chemotherapy, OR was 2.6 (95% CI, 1.03-6.41; P = .043). The OR for weight loss in Stage III breast cancer was 12.5 (95% CI, 1.21-128.84; P = .034) and 4.3 (CI, 1.07-17.24; P = .40) for comorbidity. Results demonstrate that weight changes in a pooled sample are overestimated. However, premenopausal women receiving anthracycline-based chemotherapy show a tendency toward a body composition with increasing fat mass. A scheduled assessment of changes in weight and body composition is relevant at 18 months after treatment. To compare future studies, common measuring and cutoff points are needed.

Economic evaluation of bone stimulation modalities: A systematic review of the literature.

PubMed

Button, Melissa L; Sprague, Sheila; Gharsaa, Osama; Latouche, Sandra; Bhandari, Mohit

2009-04-01

Various bone stimulation modalities are commonly used in treatment of fresh fractures and nonunions; however, the effectiveness and efficiency of these modalities remain uncertain. A systematic review of trials evaluating the clinical and economical outcomes of ultrasounds, electrical stimulation, and extracorporeal sound waves on fracture healing was conducted. We searched four electronic databases for economic evaluations that assessed bone stimulation modalities using ultrasound therapy, electrical stimulation, or extracorporeal shock waves. In addition, we searched the references and related articles of eligible studies, and a content expert was contacted. Information on the clinical and economical outcomes of patients was independently extracted by reviewers. Fourteen studies met the inclusion criteria; therefore, very limited research was found on the cost associated with treatments and the corresponding outcomes. The data available focus primarily on the efficacy of newly introduced treatment methods for bone growth, but failed to incorporate the costs of implementing such treatments. One economic analysis was identified that assessed different treatment paths using ultrasound. A total cost savings of 24-40% per patient occurred when ultrasound was used for fresh fractures and nonunions (grade C recommendation). The results suggest that the ultrasound is a viable alternative for bone stimulation; however, the impacts of the other modalities are left unknown due to the lack of research available. Methodological limitations leave the overall economic and clinical impact of these modalities uncertain. Large, prospective, randomized controlled trials that include cost-effectiveness analyses are needed to further define the clinical effectiveness and financial burden associated with bone stimulation modalities.

Cognitive function in postmenopausal women receiving adjuvant letrozole or tamoxifen for breast cancer in the BIG 1-98 randomized trial

PubMed Central

Phillips, Kelly Anne; Ribi, Karin; Sun, Zhuoxin; Stephens, Alisa; Thompson, Alastair; Harvey, Vernon; Thürlimann, Beat; Cardoso, Fatima; Pagani, Olivia; Coates, Alan S.; Goldhirsch, Aron; Price, Karen N.; Gelber, Richard D.; Bernhard, Jürg

2010-01-01

Summary Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant A) 5-years tamoxifen, B) 5-years letrozole, C) 2-years tamoxifen followed by 3-years letrozole, or D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B+C; N=65) versus tamoxifen (A+D; N=55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z-scores =0.28, p=0.04, 95% CI:0.02, 0.54, Cohen's D = 0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen. PMID:20385495

Adjuvant chemotherapy for breast cancer and cognitive impairment.

PubMed

Marín, Alvaro Pinto; Sánchez, Andrés Redondo; Arranz, Enrique Espinosa; Auñón, Pilar Zamora; Barón, Manuel González

2009-09-01

Complaints of loss of memory and lack of concentration have been reported by long-term survivors of breast cancer. This mild cognitive impairment (MCI), also called "chemobrain" or "chemofog," has been the subject of a number of studies in the last few years. This cognitive impairment, although usually mild, must be studied to define possible risk factors for its development, and for future research into a preventive or therapeutic treatment approach. Long-term survivors of breast cancer must be followed to detect possible treatment sequelae as soon as possible. Since the number of these long-term survivors has increased in the last years, in part because of more active adjuvant treatments, our knowledge about the long-term side effects of these therapies has also grown.

Coca (Erythroxylum coca) Control is Affected by Glyphosate Formulations and Adjuvants.

PubMed

Marshall, E J P; Solomon, Keith R; Carrasquilla, Gabriel

2009-01-01

The aerial spray program for the eradication of coca in Colombia uses Glyphos, a local formulation of glyphosate tank-mixed with an adjuvant product, Cosmo-Flux. There are some potential risks to amphibians from direct overspraying of shallow waters. In order to evaluate potential alternative mixtures, a field experiment was conducted at the Center of National Training of Police Operations in Tolima province, Colombia. Plants of coca were established with irrigation and grown to 75 cm tall. A randomized split-plot design experiment was laid out and sprayed with a range of glyphosate formulations and different adjuvants using an experimental ground sprayer. Assessments were made of plant vigor, height, and above-ground standing crop (fresh weight) 3 wk after application. Resprouting of plants was assessed at 9 wk after treatment. Unformulated glyphosate applied as the product Rodeo gave poorer control of coca than two formulated products, Roundup Biactive (from Europe) and Colombian Glyphos. In general, these products performed well without added adjuvants, giving control similar to that of the eradication mixture with Cosmo-Flux. There was some evidence that addition of the adjuvant Silwet L-77 and to a lesser extent Mixture B (from the United Kingdom) gave more rapid herbicide symptoms. There were also indications that glyphosate rates of less than 3.69 kg acid equivalents (a.e.)/ha could give control in the range of 95%. Depending on the environmental risk requirements, the experiment indicates that, should other spray mixtures be required, there are potential alternatives. These would require extensive field testing to cover different environmental conditions, different coca varieties, and particularly aerial application, prior to a recommendation. Should the glyphosate product require changing, Roundup Biactive may be considered. Should the adjuvant require changing, then on the basis of this research, Silwet L-77 and Mixture B would be good candidates for

Antibody-Antigen-Adjuvant Conjugates Enable Co-Delivery of Antigen and Adjuvant to Dendritic Cells in Cis but Only Have Partial Targeting Specificity

PubMed Central

Abuknesha, Ram; Uematsu, Satoshi; Akira, Shizuo; Nestle, Frank O.; Diebold, Sandra S.

2012-01-01

Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC) that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA) and CpG oligodeoxynucleotides (ODN). We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL) responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses. PMID:22808118

Adjuvant treatment of resectable biliary tract cancer with cisplatin plus gemcitabine: A prospective single center phase II study.

PubMed

Siebenhüner, Alexander R; Seifert, Heike; Bachmann, Helga; Seifert, Burkhardt; Winder, Thomas; Feilchenfeldt, Jonas; Breitenstein, Stefan; Clavien, Pierre-Alain; Stupp, Roger; Knuth, Alexander; Pestalozzi, Bernhard; Samaras, Panagiotis

2018-01-11

Biliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant treatment in patients with resected BTC. Patients initially received gemcitabine 1000 mg/m 2 alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m 2 and cisplatin 25 mg/m 2 on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed. Overall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a corresponding 3-year DFS of 43.1 ± 9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8-62.3) with a 3-year

Cytokine-enhanced vaccine and suicide gene therapy as surgery adjuvant treatments for spontaneous canine melanoma: 9 years of follow-up.

PubMed

Finocchiaro, L M E; Glikin, G C

2012-12-01

We present here the updated results after 9 years of the beginning of a trial on canine patients with malignant melanoma. This surgery adjuvant approach combined local suicide gene therapy with a subcutaneous vaccine composed by tumor cells extracts and xenogeneic cells producing human interleukin-2 and granulocyte-macrophage colony-stimulating factor. Toxicity was absent or minimal in all patients (0≤VCOG-CTCAE grade≤1). With respect to surgery-treated controls (ST), the complete surgery (CS) arm of this combined treatment (CT) significantly increased the fraction of local disease-free patients from 13 to 81% and distant metastases free from 32 to 84%. Even though less effective than the CS arm, the partial surgery (PS) arm of this CT was significantly better controlling the disease than only surgery (14% while PS-ST: 0%, P<0.01 and CS-ST: 5%, P<0.05). In addition, CT produced a significant sevenfold (CS) and threefold (PS) increase in overall survival. The CS-CT arm significantly improved both CS-ST metastasis-free- and melanoma overall survival from 99 days (respective ranges: 11-563 and 10-568) to >2848 days (81-2848 and 35-2848). Thus, more of 50% of our CT patients died of melanoma unrelated causes, transforming a lethal disease into a chronic one. Finally, surgery adjuvant CT delayed or prevented post-surgical recurrence and distant metastasis, significantly improved disease-free and overall survival maintaining the quality of life. Long-term safety and efficacy of this treatment are supported by the high number of CT patients (283) and extensive follow-up (>9 years). The successful clinical outcome encourages the further translation of similar approaches to human gene therapy trials.

Axillary hyperhidrosis: A review of the extent of the problem and treatment modalities.

PubMed

Singh, Sanjay; Davis, Harriet; Wilson, Paul

2015-10-01

The purpose of this review is to summarize the extent of the problem of axillary hyperhidrosis and treatment modalities available. The benefits and disadvantages of various treatments are reflected on with the hope of providing a starting point to investigate new ways of treating hyperhidrosis. A literature search was conducted using various databases and search criteria. Current treatments include aluminium chloride antiperspirants, iontophoresis, botox injections and endoscopic thoracic sympathectomy. Botox therapy is usually the most effective treatment, without surgery or unpleasant side effects. However it has to be administered by a skilled clinician and involves around 20 injections to treat axillary hyperhidrosis. Other ways of giving Botox are being developed, the most promising one being the use of microneedles which are able to penetrate the skin and deliver drugs to the target area of the dermis without causing pain. In comparison to the temporary effects of microneedles, laser and microwave therapies are also assessed as they offer the hope of permanent relief from hyperhidrosis. There is a considerable dearth in the literature on the management of axillary hyperhidrosis. Further study in larger populations with longer follow up times is critical to access the long term effects of treatment. Microneedles could be the future treatment of choice with the potential to deliver drugs in a safe and pain free way. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Editorial - Avoiding unethical Helicobacter pylori clinical trials: Susceptibility-based studies and probiotics as adjuvants